Keywords: Spectroscopy, Neuro, early-life stress, adverse childhood experiences, age-related, brain metabolites

Motivation: Adversity experienced during early life termed early-life stress (ELS) might increase the risk for neuroinflammation and neurodegenerative disorders in the adult human brain. An enhanced understanding of these relationships will aid in diagnosis and intervention.

Goal(s): Our goal was to investigate whether ELS is associated with changes in brain metabolism by using ¹H MR spectroscopy.

Approach: The interaction between metabolite concentrations obtained from MRS, acquired in adult women, age, and scores of ELS was modeled using non-linear statistics.

Results: Higher concentrations with increasing age in individuals exposed to ELS were found for specific metabolites suggesting long-term effects of ELS on the human brain.

Impact: Understanding the role of early-life stress (ELS) in driving neuroinflammatory processes and identification of specific biomarkers to assess the risk for accelerated cognitive decline and neurodegenerative disorders in individuals exposed to ELS will aid in early identification and targeted interventions.

Keywords: Spectroscopy, Data Analysis, Neurochemical Concentration Quantification

Motivation: Current methods to quantify neurochemical concentrations in magnetic resonance spectroscopy (MRS) assume an equal distribution of neurochemicals between white matter (WM) and grey matter (GM), however, the implications of this assumption have not been explored.

Goal(s): We aimed to improve the accuracy of MRS concentration measures by replacing assumptions with calculated values.

Approach: We compared calculated concentration ratios of six neurochemicals in WM and GM with the assumed 1:1 ratio to determine the impact of assuming a 1:1 ratio on neurochemical concentrations.

Results: The 1:1 ratio assumption yielded estimate errors of up to 55%.

Impact: Implementation of our calculated white and grey matter neurochemical distributions will yield magnetic resonance spectroscopy concentration measures that are ~30-55% more accurate than conventional methods.

Keywords: Spectroscopy, Spectroscopy, High-field MRI, Peripheral nerve, Neuroscience, Brain

Motivation: Transcutaneous auricular vagus nerve stimulation (taVNS) has shown therapeutic efficacy in treating conditions such as epilepsy and depression. Recently, its potential to improve cognitive performance in healthy adults has been explored.

Goal(s): However, little is known about the neurochemical processes underlying performance enhancing outcomes. This study assessed immediate and residual effects of taVNS on neurochemical activity in brain regions associated with attention, vigilance, and stress.

Approach: Magnetic resonance spectroscopy was used to non-invasively quantify neurochemical responses immediately after and 60 minutes post-stimulation compared with baseline.

Results: Increased myo-inositol was observed in the posterior cingulate immediately after taVNS but not sustained for 60 minutes.

Impact: Using magnetic resonance spectroscopy allowed for the evaluation of the short-term neurochemical response across multiple brain regions from transcutaneous auricular vagus nerve stimulation, which helps elucidate the mechanisms of the potential therapeutic and performance-improvement effects achieved from stimulation

Keywords: Spectroscopy, Tumor, Glioma, 5-ALA

Motivation: Heterogeneity in gliomas represents a clinical and diagnostic issue. 5-ALA fluorescence used for intraoperative tumor delineation is different depending on the tumor type. Understanding the dysregulations in the heme pathway using 7T MRSI could help understanding metabolic heterogeneity in tumors.

Goal(s): Identifying 7T MRSI metabolites useful for investigating mechanisms of 5-ALA fluorescence and preoperative tumor characterization.

Approach: We retrospectively correlated 5-ALA fluorescence from clinical reports to metabolic ratios from  7T MRSI scans in a cohort of 23 patients.

Results: 5-ALA correlated with the Gln/tCr ratio (r²=0.597), which also correlated with the tumor grade.

Impact: Using 7T MRSI and 5-ALA, we improve guidance for neurosurgeons to resect aggressive tumor hotpots. Furthermore, 7T MRSI could be useful for in vivo studies of metabolic disturbances involved in 5-ALA activation.

Keywords: Spectroscopy, Molecular Imaging, functional MRS, schizophrenia, redox, glutathione

Motivation: Redox imbalance in schizophrenia may help to explain the full range of observable schizophrenia symptoms.

Goal(s): Our goal was to use a more appropriate tool to measure dynamic changes in neurometabolites in schizophrenia compared to traditional MRS techniques.

Approach: We used functional MRS with a cognitive Stroop task to investigate glutathione dynamics as well as associated glutamate and glutamine dynamics.

Results: Glutathione levels increased during task and stayed elevated for healthy subjects, but not for patients.

Impact: By demonstrating abnormal anterior cingulate cortex glutathione response to short-term cognitive battery in first-episode schizophrenia, we offer novel support and added framework behind potential redox imbalances in schizophrenia and their utility in managing symptom treatment.

Keywords: Spectroscopy, Spectroscopy, MRSI, UHF, PRESS, FID

Motivation: Valuable in the preclinical realm, Magnetic Resonance Spectroscopic Imaging encounters issues with long acquisition time and low signal-to-noise ratio. Numerous excitation schemes allow for metabolic mapping.  

Goal(s): The current study aims at comparing, with relevant quality metrics, preclinical application of two ¹H-MRSI localization schemes at 14.1T: FID-MRSI and PRESS-MRSI.

Approach: Both FID and PRESS-MRSI datasets were acquired on the rodent brain in identical conditions (n=3) and processed using the same workflow for objective analysis. 

Results: An increased coverage and SNR per unit of time were observed for FID-MRSI. Both methods reached similar quantitative results for two different brain regions. 

Impact: Objective assessment of preclinical ¹H-FID and ¹H-PRESS-MRSI allows for exploration of their respective limitations and optimization of both localization schemes for different case studies found in preclinical research.

Keywords: Spectroscopy, Osteoarthritis, Chronic Pain

Motivation: Alterations in the brain are suggested to contribute to chronic arthritis pain, however there is limited research on the specific neurochemicals and brain regions involved in this process.

Goal(s): We aimed to identify neurochemicals and brain regions associated with chronic pain in knee osteoarthritis to understand the brain’s contribution to this condition.

Approach: We used magnetic resonance spectroscopy to compare neurochemical levels in four pain-related brain regions between cohorts of patients with painful knee osteoarthritis and healthy controls.

Results: Significantly lower levels of GABA and myoinositol in the anterior cingulate cortex in the knee osteoarthritis group suggests potential disrupted inhibitory processes and neuroinflammation.

Impact: Patients with painful knee osteoarthritis exhibited significantly lower levels of GABA and myoinositol in the anterior cingulate cortex compared to healthy controls. These findings illuminate the anterior cingulate cortex as a potential therapeutic target for knee osteoarthritis pain management.

Keywords: Spectroscopy, Spectroscopy, Skeletal muscle, SVS, pulse sequence

Motivation: Due to the dependence on the type and orientation of the skeletal muscle, it is a challenge to perform ¹H MRS to characterize the muscle features in this highly organized structure.

Goal(s): The aim of this work was to implement a non-water-suppressed semi-LASER (sLASER) sequence to characterize up- and downfield metabolites in human skeletal muscle in vivo at 3T. 

Approach: This was achieved through optimizing the crusher scheme and phase cycling schemes in sLASER and combining it with metabolite cycled.

Results: High quality spectra were obtained from different muscle fibers of 8 healthy volunteers to characterize both up- and downfield metabolites.

Impact: We demonstrated the application of metabolite-cycled semi-LASER spectroscopy in human skeletal muscles at 3T. Up- and downfield parts of the spectrum were detected with high quality enabling the detection of important metabolites including carnosine providing unique insight into human physiology.

Keywords: Spectroscopy, Spectroscopy, Water referencing

Motivation: Absolute quantification of the 1H MRS metabolites remains a challenge for 2D MRSI, due to long acquisition times for the unsuppressed water reference and the multiple biases present due to relaxation and inhomogeneity.
 

Goal(s): To propose a water reference method combining single voxel STEAM and quantitative MRI (qMRI).

 

Approach: The method is demonstrated and tested against a standard water referencing method on one healthy subject. Its application is demonstrated in a brain tumor patient.
 

Results: Apart from obtaining absolute metabolite concentrations, corrected for all water relaxation times, 4 qMRI maps (PD, T1, T2* and QSM) maps are also generated.

Impact: We propose a method for absolute quantification of cerebral metabolites in 2D MRSI by combining STEAM and quantitative MRI. The method is tested against a reference method in a healthy subject and its application demonstrated for a brain tumor patient.

Keywords: Spectroscopy, Spectroscopy, 1H MRS, fMRS, OCD

Motivation: The neurobiological mechanisms of poor top-down motor control in OCD are not well understood.

Goal(s): Our goal was to investigate neurobiological differences in glutamate modulation across different motor/inhibitory control responses in OCD compared to healthy controls.

Approach: ¹H fMRS was conducted in adolescents with OCD and healthy controls.

Results: Task-specific impairments to the dACC glutamate modulation were observed in OCD compared to healthy controls.

Impact: These results providing compelling evidence towards characterizing neurosignaling changes in OCD pathophysiology.

Keywords: Spectroscopy, Molecular Imaging, GABA, Spectral editing, MRSI

Motivation: Robust B0 and B1+ detection of GABA+ and Glx in 3D or whole brain MRSI using spectral editing is challenging at 7T.

Goal(s): To simultaneously detect GABA+ and Glx in multi-regions and generate 3D maps using SLOW-editing for human brain at 7T.

Approach: SLOW-EPSI was performed on 5 healthy volunteers.

Results: Our method is robust to [-0.3 ppm, +0.3 ppm] B0 and [40%, 250%] B1+ for GABA+/Glx editing. 9-minute acquisition is sufficient for any arbitrarily shaped volume quantification. 18-27 minutes acquisition is sufficient for 3D mapping of GABA+. 9-18 minutes acquisition is sufficient for 3D mapping of Glx.

Impact: Our work presents a large 3D or whole-brain MRSI tool for GABA+ and Glx quantification and mapping at 7T, which allows clinicians to examine changes in GABA+ and Glx in the brain for any arbitrarily shaped volume.

Keywords: Spectroscopy, Spectroscopy, fMRS, 1H MRS

Motivation: The neurobiological mechanisms involved in poor weight loss maintenance are not understood.

Goal(s): Our goal was to investigate neurobiological differences in glutamate modulation across different motor/inhibitory control responses after completion of a clinical weight loss program. 

Approach: ¹H fMRS was conducted in a pilot sample who had completed a clinical weight loss program.

Results: The presence of food cues as the stimuli influenced the glutamate modulation during inhibitory control responses. 

Impact: With further investigation, our preliminary evidence of a food-cue specific difference in glutamate modulation may fuel better treatment plans to support more successful maintenance of weight loss.

Keywords: Spectroscopy, Spectroscopy, Succinate

Motivation: To measure succinate in brain during circulatory arrest in a piglet model of cardiac bypass.

Goal(s): Dynamic measurement of succinate using 3T MR spectroscopy

Approach: Spectral fits of the archived data were used to create dynamic plots of succinate, to provide statistics, and to generate simulated spectra for validation. 

Results: Elevation of succinate during circulatory arrest was observed and validated. Fitting bias was evaluated over the linewidths and signal-to-noise S/Ns of the archived data. Succinate increase did not appear to be dependent on bypass temperature. Succinate elevation was not observed with antegrade cerebral perfusion.

Impact: Elevated succinate during ischemia has been identified as a source of ischemic-reperfusion injury. The ability to measure increased succinate during ischemia plus the ability to intercede with succinate inhibitors may have important consequence prior to re-perfusion in bypass and stroke.

Keywords: Spectroscopy, Spectroscopy, Glioma, IDH mutation, brain metabolites, ROC analysis, diagnosis

Motivation: Reliable noninvasive quantification of D-2-hydroxyglutarate (2HG) for diagnosis of isocitrate dehydrogenase (IDH)-mutant gliomas is challenging.

Goal(s): To discriminate between IDH-mutant and wild-type gliomas based on their full metabolic profile.

Approach: Partial Least Squares Discriminant Analysis (PLS-DA) was used to discriminate IDH-mutants from wild-types using in vivo 3T MRS data from 47 patients with a newly diagnosed glioma.

Results: Higher 2HG and lower glutamate + glutamine, glutamate, glycine, and glutathione were observed in IDH-mutants compared to wild-types. The PLS-DA model showed higher accuracy (AUC = 0.949) compared to 2HG alone (AUC = 0.753), underscoring the superiority of a comprehensive approach over single metabolite analysis.

Impact: Exploring in vivo metabolic alterations beyond D-2-hydroxyglutarate is crucial for enhancing diagnostic accuracy in detection of IDH mutations in patients with gliomas, as well as for a deeper understanding of the fundamental biological consequences of this mutation.

Keywords: Spectroscopy, Spectroscopy, sLASER, STEAM, 3T and 7T, Longitudinal Reproducibility, High-Field MRI, Ultrahigh-Field MRI, Magnetic Resonance Spectroscopy

Motivation: The test-retest of STEAM and sLASER at both fields using the same subjects has not been investigated.

Goal(s): The aim was to evaluate the reliability using Intraclass Correlation Coefficients(ICC) and reproducibility using Coefficient of Variations (CV%) of Glutamate, Glutamine, and N-acetyl-aspartate quantification at 3T and 7T in the human motor cortex using sLASER and STEAM sequences.

Approach: Subjects were scanned a week apart using both sequences at both field strengths. Voxel locations were in Paracentral Lobule (PCL) and Precentral Gyrus (PrCG).

Results: sLASER, particularly at 7T, demonstrated superior performance in both regions within a reasonable timeframe,making it the recommended sequence for longitudinal studies. 
 

 

Impact: This study’s findings offer valuable insights for researchers conducting longitudinal studies using MRS. The improved reliability and reproducibility of the sLASER technique, particularly at 7T, enable more precise tracking of disease progression, potentially leading to improved disease tracking. 

Keywords: Spectroscopy, Spectroscopy, 7T ultra high field MRS, Cognition

Motivation: This study aims to contribute novel insights into the potential cognitive role of myo-inositol and its implications for brain metabolism using 7 Tesla magnetic resonance spectroscopy (7T-MRS).

Goal(s): Our primary goal was to determine if myo-inositol concentrations within the posterior cingulate cortex (PCC) influence cognitive performance.

Approach: Ultra-high field 7T-MRS was used to measure myo-inositol concentrations in relation to cognitive performance, as assessed with the Trail-Making-Test (TMT-A/B). Data analysis involved multiple linear regressions with covariate control and bootstrapping for robustness.

Results: Our study reveals a significant (p<0.05) positive association between higher myo-inositol levels in the PCC and enhanced cognitive performance in TMT-A/B.

Impact: This study suggests the potential of myo-inositol as a biomarker for cognitive functioning. Furthermore, the findings contribute to our understanding of brain neurochemistry, supporting the advancement of personalised medicine for cognitive impairments.

Keywords: Spectroscopy, Spectroscopy, Machine Learning/Artificial Intelligence, Artifacts, Data Processing, Software Tools, Simulations, Brain, Pediatric

Motivation: GABA-edited MRS suffers from data quality challenges due to its low signal to noise ratio (SNR). 

Goal(s): We propose an automated labeling algorithm for transient quality and a dual-domain deep learning model for filtering spectra transients based on quality.  

Approach: We trained our model with simulated data containing commonly occurring artifacts labelled with our continuous automated labelling algorithm which ranges from –1 (poor quality) to +1 (good quality). We subsequently evaluated our model’s performance by removing (filtering) poor quality transients corresponding to quality values less than 0. 

Results: Our model outperformed qualitatively simple averaging using all collected transients for 70-80% of scans.

Impact: Our model can successfully assign a continuous quality score between –1 (poor) and +1 (good) to GABA-edited MRS difference data (i.e., a single ON-OFF edit pair) which when used for filtering, improves MRS quality metrics compared to simple transient averaging.   

Keywords: Spectroscopy, Spectroscopy, MRSI, Acquisition Delay, FID-MRSI, Ultra-high field, Preclinical, Rat

Motivation: ¹H Free-Induction Decay (FID) MRSI is limited by the acquisition delay (AD) between the RF excitation pulse and the FID signal. N initial data points are thus lost.

Goal(s): Our goal was to evaluate the consistency of the Backward Linear Prediction (BLP) auto-regressive reconstruction method to recover the lost FID data points.

Approach: In-vivo rat data were used to investigate the impact of the BLP methodology in a cut-and-recover approach; further Monte-Carlo simulations were used to identify the method validity limit.

Results: In-vivo and Monte-Carlo results highlighted the consistency of the BLP methodology for realistic FID reconstruction ranges.

Impact: Focusing on metabolites of interest, no significant variations of brain map concentrations have been detected between original FID acquisitions and BLP reconstruction outcomes between AD=1.3ms and AD=0.708ms. Moreover, Monte Carlo simulations showed good quantification reliability until AD=2.7 ms.

Keywords: Spectroscopy, Spectroscopy, MRSI, UHF, Compressed Sensing

Motivation: Preclinical Magnetic Resonance Spectroscopic Imaging offers valuable spatial information about metabolite content in the rodent brain, but is subjected to low signal-to-noise ratio and long acquisition time.

Goal(s): Our goal was to accelerate preclinical ¹H-MRSI by implementing and validating compressed sensing acceleration schemes to enable accurate acquisitions under 10 minutes.

Approach: Free Induction Decay MRSI sets were acquired on the rodent brain using compressed sensing with different acceleration factors and k-space center acquired volumes.

Results: Metabolic maps and regional differences were preserved with higher acceleration factors, going from 13 minutes to 6.5 minutes acquisition and lower.

Impact: 1H-MRSI using compressed sensing, with its achieved 6.5 minutes acquisition, could be used for effective and reliable transversal metabolic studies of neurodegenerative diseases within preclinical models, such as the bile duct ligation rat model for hepatic encephalopathy. 

Keywords: Spectroscopy, Metabolism, GABA, Spectral editing, MRSI

Motivation: Developed initially for 7T scanners, the widespread inaccessibility of such MRI systems underscores the urgent need to adapt SLOW-editing for more commonly available 3T field strengths.

Goal(s): Our primary goal is to detect metabolites like 2HG, GABA, and Glx using SLOW-editing at 3T, effectively addressing water/lipid suppression challenge.

Approach: We utilized symmetric and asymmetric CHEmical-shifted selective Adiabatic Pulses (CHEAP) in conjunction with a 3D Echo-Planar Spectroscopic Imaging (EPSI) readout sequence.

Results: Our investigations confirm the feasibility of employing SLOW-editing in conjunction with the EPSI sequence for spectral editing of GABA+ and Glx, validated through in vitro and in vivo experiments.

Impact: This work demonstrates that SLOW-EPSI can be employed for spectral editing of low concentration metabolites, including 2HG, GABA and Glx, on a 3T MR scanner for 3D/whole-brain MRSI.

Keywords: High-Field MRI, Spectroscopy, Downfield, Human brain

Motivation: Downfield (DF) MR spectroscopic imaging (MRSI) is a promising new metabolic imaging technique that has previously been demonstrated in the human brain at 3T. This abstract describes initial results of 3D DF-MRSI at 7T.

Goal(s): To implement and test 3D DF-MRSI at 7T.

Approach: The 3D DF-MRSI pulse sequence was adapted for 7T and tested on 4 healthy volunteers.

Results: High-field DF-MRSI with 0.7 mm³ nominal voxel resolution is feasible. Concentration and uncertainty estimates for the 9 downfield peaks and combined amide resonances from selected voxels were not significantly different, except for DF6.83 which was significantly lower in the CSO than DLPFC (p=0.007).

Impact: High-field DF-MRSI should now be able to spatially map the exchangeable protons in human brain within clinically acceptable times and accuracy to be used in future studies of brain tumors or other neuropathological disorders.

Keywords: Spectroscopy, Brain, MRSI

Motivation: To provide a metabolic reference atlas for brain metabolite concentrations. 

Goal(s): Derive regional metabolite concentration estimates from the human brain. 

Approach: Brain 1H MRSI data were acquired from 10 healthy controls and quantitative metabolite maps were combined via transformation into MNI space to derive median metabolite maps. Regional metabolite concentration estimates were derived. 

Results: Brain metabolite maps and regional concentrations for 12 human brain metabolites have been derived. 

Impact: A reference standard for metabolic brain MRI was established. 

Keywords: Spectroscopy, Spectroscopy

Motivation: The study addresses a gap in literature concerning the impact of spectral linewidth and lineshape differences on GABA+ estimates.

Goal(s): To assess the degree to which differences in linewidth/lineshape may confound GABA+ estimates.

Approach: In-vivo GABA+-edited spectra (N=222) were quantified with six modelling algorithms after applying varying degrees of Lorentzian and Gaussian linebroadening.

Results: Most algorithms showed strong negative associations between amount of Lorentzian linebroadening and GABA+ estimate (2-5% per Hz LB), consistently across datasets. Gaussian linebroadening showed contrasting, substantially weaker associations.
In functional applications and cases of differing T2 relaxation between regions or subject groups, these results indicate a potentially significant confound.

Impact: Comparing metabolite concentration estimates across different anatomical regions, subject groups or experimental conditions requires appropriate handling of differences in linewidth and linebroadening mechanisms. We demonstrate that several modelling algorithms have linebroadening biases, differing by lineshape, that may confound findings.

Keywords: Spectroscopy, Spectroscopy

Motivation: Preprocessing of MRS data is important in order to improve the spectral quality.

Goal(s): Here we propose a novel approach to simultaneously correct for frequency and phase drifts using cross-correlation technique.

Approach: Random frequency and phase offsets were added to a previously acquired STEAM human data at 7T at two different noise levels.

Results: Results show that the proposed technique can accurately correct for both small and large frequency (<50 Hz) and phase drifts (±40 deg) even at low SNR levels. The technique was successfully demonstrated in a noisy MRS dataset acquired from a small volume-of-interest in the mouse brain.

Impact: A fast and robust technique which accurately correct for both small and large frequency and phase shifts in MRS data.

Keywords: Spectroscopy, New Signal Preparation Schemes, Magnetic Resonance Spectroscopy, Macromolecules

Motivation: A new water suppression module optimized for both macromolecule detection and short repetition time sequences such as magnetic resonance spectroscopic imaging.

Goal(s): To have an efficient, flexible, water suppression algorithm where macromolecules can be measured.

Approach: Single voxel localization by adiabatic selective refocusing (semi-LASER) measurement of macromolecules were conducted in the prefrontal cortex, posterior frontal (PFL) and occipital lobes. Both VAPOR and the customizable water suppression (COWS) algorithm were performed for each experiment.

Results: Both WS methods performed well with residual water signals below the 2.01-ppm NAA singlet signals. COWS demonstrated better water suppression than VAPOR overall, especially in the PFL.

Impact: A new customizable water suppression algorithm, COWS, was tested in vivo for improved efficiency and speed when compared to the gold standard (VAPOR).

Keywords: Spectroscopy, Brain, 7T, Neuro, MRSI, Reproducibility

Motivation: 1H FID-CRT-MRSI at 7T is a promising approach for non-invasive quantification of metabolic processes in the brain. Its medium-term reproducibility has never been investigated even though it is a requirement for many potential study setups.

Goal(s): To evaluate the intersession reproducibility of 1H FID-CRT-MRSI at 7T.

Approach: We calculated metabolite concentration estimates in 55 brain regions for two measurement sessions one week apart, and determined coefficients of variations between them.

Results: We found good overall reproducibility, with CVs ranging from 7.5% to 12% for different brain regions, and concentration estimates matching our previous work.

Impact: We established good reproducibility of FID-CRT-MRSI at 7T, enabling longitudinal study setups e.g. for disease monitoring. Another potential follow-up of this work may be tracking the intra-day metabolite level variations in the brain in a non-invasive way.

Keywords: Spectroscopy, Spectroscopy

Motivation: NAD⁺ and tryptophan are important in energy metabolism, DNA repair, mitochondrial function, and aging. Both have recently been observed in brain at 7T, but observation at 3T is more challenging and has not been shown previously.

Goal(s): To detect NAD⁺ and tryptophan at 3T in brain in a clinically feasible scan time less than 5 minutes.

Approach: A single slice spectroscopy sequence with spectrally selective excitation was developed and optimized, allowing high sensitivity acquisition.

Results: The H2 (9.3 ppm) and H6 (9.1 ppm) peaks of NAD⁺ and the indole (10.1 ppm) peak of tryptophan are both unambiguously observed in four healthy subjects.

Impact: The ability to identify NAD+ and tryptophan at 3T in less than 5 minutes has the potential to significantly enhance the adoption of this method as part of existing neuroimaging protocols.

Keywords: Spectroscopy, High-Field MRI

Motivation: Hepatic choline-containing compounds (CCC) are an important biomarker of metabolic health.

Goal(s): The aim of this work is to measure the concentration of fat and choline-containing compounds in the liver using water-suppression cycled (WSC) and water suppressed (WS) spectroscopy at 7T.

Approach: Livers of seven healthy volunteers were scanned using water-suppression cycling and the results were compared with standard water-suppressed acquisitions.

Results: Similar concentrations of CCC were reported for both techniques, with WSC providing somewhat narrower line widths. Hepatic fat fractions were also very close using each method validating WSC as a method for use at 7T.

Impact: Frequency-aligned spectra from water-suppression cycled acquisitions enable the quantification of low-concentration metabolites in vivo at 7T.

Keywords: Spectroscopy, High-Field MRI, Metabolism, Neuro

Motivation: 7T MRI is adversely affected by inhomogeneity in the B₁ transmit field. In MRSI applications, this can manifest as spatial variability in water-suppression and signal excitation, which may adversely affect quantification. 

Goal(s): To use B₁⁺ shimming to decrease the inhomogeneity of the transmit field and improve water suppression and metabolite quantification in RS-COKE MRSI. 

Approach: B₁⁺ shim weights for all RF pulses were optimised using magnitude least-squares and data compared with a circularly polarised mode acquisition. 

Results: Metabolite quantification showed greater consistency, lower error estimates and improved water-suppression efficiency, in some subjects, when B₁⁺ shimming was applied to the RS-COKE MRSI sequence.

Impact: The use of B₁⁺ shimming in RS-COKE MRSI improves the quantification of metabolite concentrations in some subjects. This increased robustness will allow for its application to patient populations in future clinical research.

Keywords: Spectroscopy, Spectroscopy

Motivation: Nuisance signal contamination and challenges associated with implementation involving advanced RF pulses and sequence hinder clinical adoption. Simplified sequence implementation and dissemination are crucial for community-driven advancement and vendor support.

Goal(s): Our goal is to integrate CHEmical-shift selective Adiabatic refocusing Pulses(CHEAP) on the Philips platform via Pulseq open-source platform, creating advanced MRSI sequences that refine metabolite analysis by minimizing unwanted signals.

Approach: Integrating chemically selective adiabatic 2𝜋-refocus pulses in Pulseq achieved optimal spectrum coverage, reducing interference from residual water and lipid signals.

Results: Implementing the CHEAP sequence significantly mitigated interference from residual water and lipid signals, demonstrating its potential for advancing MRSI.

Impact: The implementation of CHEAP sequence via Pulseq promises a standardized, shareable method, fostering collaboration and enabling precise metabolic studies. This advancement in MRS techniques may significantly improve reproducibility across sites and enhance capacity for metabolic profiling in health and disease.

Keywords: Spectroscopy, Brain, chemical shift displacement error

Motivation: Chemical shift displacement error (CSDE) and within-voxel saturation (WVS) lead to significant spatial displacement of the MRS voxel from the prescribed region and to overestimation of metabolite concentrations. 

Goal(s): To compare prospective and retrospective corrections for severe CSDE+WVS observed in standard 3T GE PRESS data. 

Approach: Prospective corrections utilize (a) removal of OVS saturation bands and (b) over-prescription of the shifted water voxel at data acquisition. Retrospective correction relies on Gasparovic’s equation and re-scaling of metabolite concentrations by the water vs. metabolite volume ratio. 

Results: Corrected concentrations agree with literature. Both corrections are applicable in multi-centre studies and laboratories with limited technical support. 

Impact: Chemical shift displacement error (CSDE) and within-voxel saturation (WVS) observed in standard 3T GE PRESS data can be corrected prospectively and retrospectively relative to data acquisition. These solutions are relevant to multi-centre studies and laboratories with limited pulse-sequence technical support.

Keywords: Spectroscopy, Spectroscopy, 3D-FID-CRT-MRSI, 3T and 7T, Longitudinal Reproducibility, High-Field MRI, Ultrahigh-Field MRI, Magnetic Resonance Spectroscopy Imaging

Motivation: A direct comparison of the longitudinal reproducibility of 3D FID-CRT-MRSI across 3T and 7T has not been performed.

Goal(s): The aim was to determine the consistency of MRSI across these two field strengths in different brain regions.

Approach: The same subjects were scanned twice within a week at both fields and intra-subject and inter-subject Coefficients of Variation (CV%) for three metabolite ratios in different brain regions were calculated.

Results: The study found high reproducibility (CVs for most ROIs <10%) for both fields. 3T can provide sufficiently reproducible results by using larger voxel sizes and shorter measurement times.

Impact: The results will impact researchers and clinicians using MRSI, providing them with a reproducible technique at a clinical field strength of 3Tand7T and can be a method for those focusing on larger brain regions or longitudinal monitoring of metabolite changes.

Keywords: Spectroscopy, Spectroscopy, MRS, T1 weighting, FSL-MRS, repetition time, TR, semi-LASER, 3T, metabolite concentration, brain, grey matter

Motivation: A short TR is often used in clinical MRS brain studies, leading to T₁-weighting of metabolites and inaccurate T₁ correction. 

Goal(s): To determine the optimal balance between scan time and TR that minimizes T₁-weighting effects when using semi-LASER MRS.

Approach: SNR and metabolite concentrations were compared for TRs of 2, 5 and 8s using FSL-MRS.

Results: A TR of 5s provides a good balance of scan time, SNR and signal recovery. For a similar scan time, TR of 2s leads to incomplete signal recovery and thus heavy T₁ weighting, while a TR of 8s results in complete signal recovery but reduced SNR.

Impact: For MRS studies using semi-LASER, our work informs scientists and clinicians on the issues of using a short TR, and recommends the optimal scan parameters to use while implementing the newly available FSL-MRS analysis package.

Keywords: Spectroscopy, Spectroscopy

Motivation: There is no standardized way of prescribing MRS voxels in the lesion. This depends entirely on the MR operator’s expertise and opinion.

Goal(s): Our goal was to analyze MRS voxel placements in brain tumors for quantitatively reliable and reproducible voxel placement.

Approach: MRS experts placed voxels and visually scored their placements. Placements and scores were compared to tumor characteristics.

Results: All experts showed a tendency to place the voxels to fill approximately 30% of voxels with tumor core for different participants. The fraction of tumor core in voxels showed a correlation of 0.76 to the fraction of tumor core in the whole tumor. 

Impact: Quantitative analysis of MRS voxel placement shows that MRS experts deemed a voxel properly placed when tumor core was adequately included, suggesting widely applicable and objective method of voxel placement and assessment for non-experts in clinical settings.

Keywords: Spectroscopy, Spectroscopy

Motivation: Navigator-based prospective motion-corrected MRS is often performed with 2^nd order shims optimized in the whole brain to prevent degradation of navigator images, resulting in suboptimal linewidth.

Goal(s): Here, we report image-based prospective motion correction with 2^nd order shims adjusted in the MRS voxel while maintaining good navigator image quality despite the strong B₀ inhomogeneity outside the voxel.

Approach: This was achieved by segmenting multislice spiral navigator images to reduce blurring artifacts from inhomogeneous B₀ fields.

Results: High-quality spectra with optimal linewidth were acquired in the presence of subject motion at 3T and 7T, demonstrating the feasibility of this new approach on clinical scanners.

Impact: Image-based prospective motion correction with optimal localized B0 shim (1st and 2nd order) in the MRS voxel is feasible in the human brain at 3T and 7T.

Keywords: Spectroscopy, Spectroscopy, LCModel

Motivation: The actual B₀ resonance field of 3T scanners is different between the three major MR vendors. 

Goal(s): Here, we report the effect on metabolite quantification of using basis sets at different B₀ fields than the B₀ frequency of the measured in vivo MRS data. 

Approach: Basis sets were simulated at thirteen different B₀ fields. Semi-LASER MRS data measured from the posterior cingulate cortex at 3T were fitted using LCModel. 

Results: Results show that biases in metabolite concentrations were within 1% when the basis set B₀ frequencies were within ±0.5 MHz from the actual scanner frequency.

Impact: A single sequence-specific basis set can be used to analyze harmonized spectroscopic data collected on clinical 3T scanners from different vendors that operate at different frequencies.

Keywords: Hyperpolarized MR (Non-Gas), Perfusion

Motivation: Hyperpolarized (HP) in vitro MRS procedures have limited throughput e.g. for drug effect monitoring and longitudinal studies.

Goal(s): Our Objective is to facilitate longitudinal HP in vitro MRS studies through rapid delivery of hyperpolarized molecules and integration of a cost-effective, continuous-flow perfusion system.

Approach: We have merged fast ¹³C SABRE-Hyperpolarization of [1-¹³C]-pyruvate-d₃ with a, budget friendly DIY system, allowing for continuous NMR tube perfusion and batch-mode injection of hyperpolarized agents.

Results: Our work demonstrates the successful detection of multiple highly polarized pyruvate injections at repetition times as short as 6 minutes, holding potential for HP agent development and studying cell metabolism under therapies.

Impact:  By combining rapid ¹³C agent hyperpolarization through SABRE with a cost-effective DIY perfusion system, our approach significantly increases the throughput and temporal resolution of hyperpolarized ¹³C MRS, unlocking new avenues for imaging agent development, metabolic studies and drug effect monitoring.

Keywords: Spectroscopy, Spectroscopy, linear-combination modeling, dynamic MRS, 2D modeling, fMRS

Motivation: Modeling and application of dynamic MRS is receiving growing interest in the community.

Goal(s): Accuracy, precision, and uncertainty of 2D modeling algorithms must be carefully characterized. 

Approach: Here, we generated synthetic spectra of an idealized (single metabolite with a stable signal across transients) conventional 1D-MRS experiment. We then compared accuracy, precision, and uncertainty estimation between a 2D model of all transients without averaging and a 1D model of the averaged spectrum.

Results: Both models performed similarly in terms of accuracy and precision.  2D-LCM afforded small benefits for uncertainty estimation for uncorrelated noise and substantial benefits for correlated noise.

Impact: For conventional (non-dynamic, multi-transient) MRS data, 2D-LCM without averaging and 1D-LCM after averaging perform similarly accurate and precise. 2D-LCM affords gains in uncertainty estimation that appear to be related to the degree of noise correlation across transients.

Keywords: Spectroscopy, Spectroscopy, Software Tools, Simulations, Artifacts, Brain

Motivation: GABA-edited Magnetic Resonance Spectroscopy (MRS) is a valuable tool used to measure GABA. However, it suffers from low signal to noise ratio. Machine learning has been recently proposed to overcome these challenges but accessing the large amount of in vivo data necessary for training can be difficult. 

Goal(s): To create a GABA-edited MRS artifact toolbox. 

Approach: We developed an open-access python toolbox to simulate four common artifacts (ghosting, eddy current effects, lipid contamination and phase/frequency shifts) in GABA-edited MRS.

Results: The toolbox will support machine learning algorithm development by complementing existing simulation software and allow for flexible user inputs for data personalization.

Impact: Our open-access python toolbox can be used to simulate spurious echoes, eddy currents, lipid contamination and motion artifacts to provide realistic and representative GABA-edited MRS data. This can be used for methods development such as training machine learning algorithms.

Keywords: Spectroscopy, Modelling, Data synthesis

Motivation: MRS data can be accurately simulated in terms of metabolite signals, but contributions from macromolecules, lipids, and scan-related imperfections are more challenging to simulate, leading to realism gaps between in-vivo and simulated spectra.
 

Goal(s): The goal is to bridge the realism gap between in-vivo and simulated MRS spectra for developing downstream deep learning applications.

Approach: We propose a physics-informed autoencoder which uses signal-based modules in the encoder and a deep learning-based decoder to generate spectra with in-vivo characteristics.

Results: Our physics-informed method effectively narrows the realism gap between in-vivo and simulated spectra with reduced reconstruction scores and increased overlap in spectral feature space.

Impact: Our research lays the foundation for a robust hybrid MRS data generation framework which generates realistic MRS data while maintaining the interpretability of physics-based simulations. It will help to generate data for developing downstream deep learning applications for MRS.

Keywords: Non-Proton, White Matter, Myelin

Motivation: Improved sensitivity to changes in myelin membranes may be achieved by phosphorous (³¹P) solid-state NMR (ssNMR), enabling more direct evaluation of neurodegeneration.

Goal(s): To demonstrate how ssNMR proton cross-polarization (CP) may be more sensitive to membrane morphology than ³¹P alone.

Approach: Using porcine neural tissue, we conducted a series of ³¹P ssNMR experiments that characterize the myelin phospholipid involvement in ³¹P-CP and CP’s sensitivity to variations in membrane composition, orientation, and dynamics.

Results: The CP signal is highly sensitive to the amount and orientation of myelin between grey and white matter samples across neural regions, and may better detect changes in membrane structure.

Impact: Improved sensitivity to subtle variations in myelin membrane morphology using the 31P ssNMR method of CP has the potential for in vivo MRI use, and could lead to earlier diagnosis, as well as enhanced disease and treatment monitoring.

Keywords: Spectroscopy, Spectroscopy, functional MRS, visual stimulation, energy metabolism, ultra-high field, 7T

Motivation: Alterations in brain nicotinamide adenine dinucleotide (NAD+) levels, as observed in aging, neurodegenerative conditions, and psychiatric disorders, necessitate an in-depth exploration of NAD's functional dynamics.

Goal(s): Investigating the feasibility of using 31P functional MRS (fMRS) at 7T to measure NAD+ dynamics during a visual stimulation task.

Approach: 32 volunteers were measured using 31P fMRS at 7T, during exposure to an established visual stimulation task.

Results: The present study provides evidence for the possibility of measuring NAD+ dynamics in the occipital lobe using 31P fMRS during a visual stimulation task. Furthermore, the use of denoising algorithms may boost sensitivity to detect functional changes.

Impact: Functional 31P MR Spectroscopy could contribute to complex cognitive and clinical studies, investigating energy metabolism deficits. Eventually, this knowledge could contribute to the development of novel therapeutic strategies targeting brain energy deficits associated with neurodegenerative diseases and cognitive impairments.

Keywords: Spectroscopy, Spectroscopy, 13C, RF coil

Motivation: Studying cerebral metabolism in the human frontal lobe using ¹³C MR spectroscopy is of great interest but presents challenges due to the low sensitivity of ¹³C nuclei and SAR limitations at ultrahigh magnetic fields.

Goal(s): Our goal was designed a 3/2-channel ¹H/¹³C RF coil specifically for conducting ¹³C MRS measurements in the human frontal lobe.

Approach: The feasibility and effectiveness of the coil design were demonstrated with bench measurements and the application of adiabatic carbon editing (ACE)-STEAM and ISIS-DEPT sequences.

Results: The coil enables the acquisition of naturally abundant ¹³C metabolite signals in both in vitro and in vivo with high sensitivity.

Impact: The 3/2-channel ¹H/¹³C RF coil, designed and optimized for ¹³C MRS study in the human frontal lobe, benefits high transmit efficiency and provides large FOV in the forehead.

Keywords: Hyperpolarized MR (Non-Gas), Metabolism, Electron Paramagnetic Resonance, Ex vivo Molecular Imaging

Motivation: Trityl radicals are the main polarizing agents used for hyperpolarization. However parallel monitoring of metabolic and redox conditions is an unmet need.

Goal(s): To use nitroxides as a polarizing agent and as a redox probe simultaneously for the same sample.

Approach: Four nitroxyl probes were tested. HyperSense DNP polarizer was used for ¹³C-pyruvate hyperpolarization.¹³C-MRS and EPR measurements were performed using same samples.

Results: CmP showed the highest hyperpolarization signal. A significant reduction in ¹³C lactate production and EPR decay rates of CmP during disease progression were confirmed.

Impact: We described successful application of nitroxyl radicals for simultaneous assessment of energy metabolism and redox status.

Keywords: Non-Proton, Non-Proton, Super-resolution, fingerprinting

Motivation: To improve resolution for translating sodium MRI into clinical practice.

Goal(s): Develop a super-resolution neural network for brain sodium images.

Approach: A cascaded Y-Net is proposed to generate high-resolution sodium images from simultaneously acquired ¹H MRF/²³Na MRI data. Human brain images from 8 healthy subjects were used for training and validation (154), and testing (22).

Results: The generated high-resolution sodium images from the Y-Net showed a structural similarity index measure (SSIM) of 0.935, a RMSE=0.034 and a PSNR=28.8 compared with the ground truth.

Impact: We introduce a Y-Net super-resolution neural network that generates high-resolution sodium images from simultaneously acquired ¹H MRF/²³Na MRI data.

Keywords: Spectroscopy, Spectroscopy

Motivation: Using single-channel transmit coils, the $$$B_1$$$ distribution is very inhomogenous in the brain. This leads to flipangle variations and consequently signal loss in a large portion of the brain. Using parallel transmit these variations might be mitigated.

Goal(s): The goal of this work is to develop universal slab-selective homogeneuos excitation pulses for whole-brain MRSI acquisitions.

Approach: Slab-selective $$$k_t$$$ points excitation have been calculated under consideration of multiple off-center frequencies. Flip angle homogeneity and excitation phase linearity was examined.

Results: Resulting spectra can be quantified using single-channel optimized basis functions. Clear gray matter white matter contrast is visible in metabolic maps

Impact: Universal excitation pulses, especially designed for whole-brain MRSI have been applied to pulse-acquire MRSI. Anatomical features could be found in the metabolic maps, even in the cerebellum. This might be a promising step towards reliable whole-brain MRSI.

Keywords: Hyperpolarized MR (Non-Gas), Cardiovascular

Motivation: Current hyperpolarized data analysis techniques, first validated for interrogating cancer, are now being utilized for HP ¹³C cardiac MRI which is metabolically diverse.

Goal(s): Our goal was to explore the viability of applying advanced data analysis techniques to previously acquired HP ¹³C cardiac data to derive novel and potentially impactful information.

Approach: We applied optimally-truncated SVD based PCA to fasted and fed state [1-¹³C] pyruvate images and k-means clustering on resulting data.

Results: Low-rank (r=3) PCA results captured sufficient data to represent the pyruvate images and identify plausible separable components of interest. Clustering spatially resolving data sufficiently for potential further constrained analyses.

Impact: Hyperpolarized ¹³C cardiac MRI can be analyzed using PCA to derive novel and potentially impactful voxel-wise analysis. As use of HP 13C MRI expands to new applications, advanced analysis techniques can be utilized to better characterize complex alterations in metabolism.

Keywords: Spectroscopy, Spectroscopy, Reproducibility

Motivation: Several consensus papers by MRS experts have addressed data collection, analysis, and reporting standards. Despite this, the usage of the MRSinMRS standardized reporting criteria remain sparsely utilized, impeding research rigor and reproducibility.

Goal(s): To overcome this, the ‘’Reproducibility Made Easy’’ software automates table population and methods section generation, streamlining the process with a single raw dataset, removing manual data entry.

Approach: We propose a tool that automatically creates a table from a single MRS raw data file, to make the process of adhering to reproducibility standards easy.

Results: The open-source ‘’Reproducibility Made Easy’’ tool can be found here: https://github.com/agudmundson/mrs_in_mrs.

Impact: Integrating the MRSinMRS Consensus Table faces challenges in parameter location within DICOM headers or MRS raw files due to nomenclature variations. "Reproducibility Made Easy" software addresses these issues, enhancing methodological transparency and standardization in research, aligning with MRSinMRS consensus principles.

Keywords: Arterial Spin Labelling, Perfusion, FAIR, whole-kidney coverage, quantitative imaging, biomarkers

Motivation: Flow-sensitive alternative inversion (FAIR) is one of the recommended arterial spin labeling (ASL) schemes for renal perfusion. Although FAIR can provide robust measurements, it suffers from partial-kidney coverage especially when aorta is close to or even at the same level of kidney in anterior-posterior (A/P) direction.

Goal(s): To obtain whole-kidney perfusion measurements using 3D FAIR despite anatomy differences within population.

Approach: Two additional labeling strategies of 3D FAIR were proposed and tested in healthy volunteers.

Results: Both strategies generated robust and high-quality perfusion maps with whole-kidney coverage within a feasible clinical scan time, which is challenging for existing 3D FAIR and pCASL implementations.

Impact: Our labeling strategies in 3D FAIR ASL could be valuable for early detection, diagnosis, differentiation, and management of renal diseases, including chronic kidney disease and acute kidney injury, despite individual anatomy differences between patients.

Keywords: Arterial Spin Labelling, Perfusion, PET/MR

Motivation: Arterial spin labeling (ASL) MRI with a single post-labeling delay may not be appropriate for quantifying cerebral blood flow (CBF) in older participants or individuals with Alzheimer’s disease (AD).

Goal(s): To evaluate reliability of multi-delay versus single-delay ASL and their associations with [¹⁵O]water positron emission tomography (PET) using simultaneous PET/MRI in older adults.

Approach: We investigated 4-week test-retest reliability using intra-class correlation (ICC) and assessed Spearman’s correlations between ASL and PET in young and older controls (n=12) and AD patients (n=3).

Results: ICC values were similar between ASL approaches but exhibited regional differences. Multi-delay ASL-based CBF was correlated with PET in more regions-of-interest.

Impact: Multi-delay arterial spin labeling MRI provides CBF measures with good intermediate-term reliability that are strongly correlated with gold-standard [15O]water PET when studying older adults and AD patients.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: We have recently shown that a PCASL-bSSFP sequence provides high quality perfusion images of the lung. However, the perfusion signal is dependent on the respective cardiac cycle.

Goal(s): Our aim was to further increase the perfusion signal of the lung parenchyma and/or to shorten the examination time using a new PCASL approach with multiple labeling.

Approach: Four volunteers were examined using an ECG-triggered multiple labeling PCASL-bSSFP sequence with different number of labeling pulses, post labeling delays and repetition delays.

Results: The PCASL sequence with multiple labeling appears to provide a higher perfusion signal of the lung parenchyma, reducing sensitivity to cardiac cycle variations.

Impact: The new PCASL approach with multiple labeling appears to provide a significantly higher perfusion signal of the lung than measurements with single labeling pulse. The sequence makes the PCASL technique more robust and faster for future application in clinical practice.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Arterial spin labeling (ASL) is vulnerable to motion and off-resonance, which may result in unstable image quality, particularly in children.

Goal(s): To propose an automatic image quality assessment model for 3D ASL in children.

Approach: The proposed model was trained and validated on 51 3D ASL scans from children, and was compared to a previously developed reference method. The performance was evaluated using AUC and 5-fold cross-validation tests.

Results: The proposed model yielded 8%-11% higher AUC, accuracy, and F1 score compared to the reference method.

Impact: The proposed model for assessing image quality in children's ASL may offer a valuable tool for clinics and studies on brain development with a large cohort.

Keywords: Arterial Spin Labelling, Arterial spin labelling, Asymmetric magnetization transfer

Motivation:  This study explores the asymmetric magnetization transfer (MT) effects on recently developed blood-brain barrier integrity (BBB-ASL) technique, with a focus on different neck labeling gradient polarities.

Goal(s): Validation of the asymmetric MT effect in BBB-ASL.

Approach: BBB-ASL parameters of arrival transit time (ATT), intra-voxel transit time (ITT), exchange time (Tex) and CBF were estimated by our custom MATLAB program based on a two-compartment model.

Results: Asymmetric MT effect changes not only depending on physical factors but also on the severity of the tissue. The difference might be related to changes in ITT and ATT.
 

Impact: This study explores the asymmetric magnetization transfer (MT) effects on BBB-ASL with MCAO model rats. Asymmetric MT effect changes not only depending on physical factors such as magnetic field inhomogeneity but also on the severity of the tissue.

Keywords: Arterial Spin Labelling, Arterial spin labelling, renal transplantation

Motivation: Renal interstitial fibrosis, a prevalent, irreversible, progressive chronic kidney injury, emerges as a crucial prognostic determinant for kidney transplantation. 

Goal(s): To explore the feasibility and performance of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after renal transplantation.

Approach: ASL was performed on 64 renal transplantation recipients. ASL parameters were obtained and analyzed.

Results: The study revealed a noteworthy negative correlation between the measured renal blood flow values, obtained through ASL, and the degree of interstitial fibrosis in transplanted kidneys. ASL can effectively differentiate various degrees of fibrosis in transplanted kidneys.

Impact: Using ASL technology, it is possible to non-invasively assess the degree of fibrotic changes in transplanted kidneys and the progression of kidney function, thereby achieving early detection, diagnosis, and treatment.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Renal imaging using echo planar imaging (EPI) readout may be sensitive to field inhomogeneities and induced ghost artifact. Besides, single inversion time is not enough for renal blood flow (RBF) quantification. Investigation of more stable clinical arterial spin label (ASL) imaging methods is required.

Goal(s): We aimed to design a stable clinical ASL sequence to quantify RBF accurately.

Approach: Multiple inversion time (TIs) readout by turbo spin echo (TSE) was processed, and the repeatability of quantification was evaluated in volunteers  (n=7).

Results: Multiple TIs combined with TSE readout of FAIR-ASL provided more accurate RBF measurement and highly repeatability compare with pcASL-EPI.

Impact: Multi-PLDs readout by TSE may provide a stable clinical ASL-FAIR sequences to accurately quantify RBF.

Keywords: Arterial Spin Labelling, Perfusion

Motivation: 3D-PCASL is a well-established perfusion MRI technique at 3T. Nonetheless, its effectiveness is hampered by increased RF power deposition at 7T limiting the SNR efficiency and labeling duration.

Goal(s): This work investigates the relationship between gray matter perfusion signal and labeling duration aiming to optimize 3D-PCASL SNR efficiency while taking into consideration the increased RF power constraints of 7T MRI.

Approach: SNR efficiency was measured at various labeling durations maintaining scan time to ~6 min and SAR to ~90% of first-level mode limit at 7T.

Results: Optimal SNR efficiency was obtained at labeling duration of ~3 s.

Impact: The result of this work provides optimal labeling duration for 7T 3D PCASL studies with maximum SNR per unit time taking into account first-level mode RF power limits.

Keywords: Arterial Spin Labelling, fMRI

Motivation: The olfactory bulbs (OBs) play a key role in the detection and processing of olfactory information. However, research on human OB function has been limited due to their challenging location for conventional T₂*-weighted BOLD fMRI. 

Goal(s): To explore ASL as an alternative to BOLD for OB functional MRI.

Approach: We utilized ASL with a 16-shot Stack-of-Spirals 3D TSE readout to obtain short-TE functional imaging. We quantified blood flow and subsequently assessed neural activation in the OB using a blocked design olfactory paradigm.

Results: This study quantifies OB blood flow for the first time and demonstrates neural activation in the OB during odor delivery.

Impact: This work highlights ASL's potential for fMRI, especially in challenging areas with high susceptibility and low signal-to-noise ratio, making it a viable option for studying olfactory-related regions where BOLD fMRI faces difficulties.

Keywords: Arterial Spin Labelling, Arterial spin labelling, infant; labeling efficiency; off-resonance

Motivation: The image quality of ASL in infants is variable.

Goal(s): To investigate the labeling efficiency in infant pCASL.

Approach: Labeling efficiency was simulated using the Bloch equation. Prospective scans were performed on 11 subjects, with pCASL at 60mm and 90mm below the AC-PC line, MRA, and B0 map.

Results: Blood flow velocity has negligible effects on the labeling efficiency at the on-resonance frequency. The combined effects of off-resonance and the high blood flow velocity are the primary cause of the variable image quality. pCASL images at 60mm showed improved SNR in 8 /11 infants, compared to that of 90mm.

Impact: This study examined the factors contributing to variable ASL images in infant and provided a preliminary solution by selecting the labeling plane.

Keywords: Arterial Spin Labelling, Perfusion, T1 mappinng

Motivation: Pseudo-continuous Arterial Spin Labeling (PCASL) MRI is a promising technique for assessing renal perfusion. Previous studies have been carried out at 1.5T and 3T field strengths, but a comparison of data acquired at both field strengths has never been performed.

Goal(s): The aim of this work was to assess the effects of field strength on the measured perfusion signal and to evaluate the reproducibility of renal PCASL at both fields

Approach: Healthy volunteers underwent repeated scans on both scanners, spaced a week apart. 

Results: The results showed excellent reproducibility and minimal differences in RBF, ATT and T1 values between visits and field strengths. 

Impact: The similarity in the study results across both field strengths underscore the potential for expanding PCASL-based renal perfusion assessment, increasing the technique accessibility, and widening diagnostic capabilities.  

Keywords: Arterial Spin Labelling, Perfusion, Arterial Spin Labelling, Normal Development

Motivation: There is lacking understanding of hemodynamic changes in children and their impact on MRI perfusion quantification.

Goal(s): We aim to investigate age-related hemodynamic changes in developing brain.

Approach: Perfusion parameters from single- and multi-delay Arterial Spin Labeling (ASL) MRI of MR-negative children are analyzed.

Results: We found significant age-dependent differences between perfusion quantification with single- and multi-delay approaches. ATT followed a non-linear distribution in age and was heterogeneous across vascular territories Our findings support the use of multi-delay ASL for improved perfusion assessment in children and provide better understanding of hemodynamic changes in developing brain.

Impact: This is the first study to investigate age-related arterial transit-time changes in children and their impact on perfusion quantification with perfusion MRI. Our findings prompt improved understanding of age-related perfusion changes and standardization of hemodynamic parameters in the pediatric cohort.

Keywords: Arterial Spin Labelling, Perfusion

Motivation: There are few validated noninvasive indicators for renal perfusion and renal function in patients with renal artery stenosis (RAS)

Goal(s): To explore the utility of arterial spin labeling (ASL) as a noninvasive indicator of renal perfusion and function in patients with RAS.

Approach: We evaluated correlations between ASL-measured preoperative renal blood flow (RBF) and renal function, then compared preoperative and postoperative RBF.

Results: ASL-measured RBF was significantly correlated with renal function. ASL was able to evaluate perfusion improvement in patients with RAS after interventional therapy.

Impact: ASL can be used as an indicator of renal function and perfusion in patients with RAS. It can also be used to assess changes in renal perfusion after interventional therapy.

Keywords: Arterial Spin Labelling, Arterial spin labelling, calibrated fMRI, BOLD, multi-echo, sequence, brain

Motivation: Calibrated fMRI quantitatively estimates cerebral metabolic rate of oxygen (CMRO2) by simultaneously measuring cerebral blood flow (CBF) with arterial spin labeling (ASL) and BOLD. Pseudo-continuous ASL (PCASL) with background suppression (BS) and 3D readout is recommended for CBF while multi-echo (ME) 2D BOLD has gained popularity. Nowadays, no calibrated fMRI sequence integrates both.

Goal(s): Our goal is to combine them in a single sequence.

Approach: We introduce a novel dual-acquisition calibrated fMRI sequence integrating BS-PCASL-3D GRASE for CBF and 2D multi-echo EPI BOLD.

Results: Resting-state data in a healthy volunteer showed CBF values concordant with literature and improved BOLD tSNR and connectivity maps.

Impact: We propose a novel sequence for calibrated fMRI that optimizes both CBF and BOLD measurements with a dual acquisition scheme, thus overcoming the limitations of previous ASL-BOLD calibrated fMRI sequences and showing promise for improved accuracy and reliability.

Keywords: Arterial Spin Labelling, Arterial spin labelling, cerebral small vessel disease

Motivation: The blood brain barrier (BBB) is damaged in patients with cerebral small vessel disease (cSVD).

Goal(s): To study the role of subtle BBB impairment in cSVD by measuring water-transport over the vessel wall.

Approach: T₂-prepared time-encoded pCASL was applied in cerebral small vessel disease (cSVD) patients and healthy controls.

Results: T₂ variations between the groups showed no significance in this preliminary sample yet. However, T₂-values tend to decay earlier in VCI patients compared to HC. This suggests earlier water-transport from blood to tissue, possibly referring to stronger BBB impairment. Moreover, broader distributions of T₂-values seem to indicate larger heterogeneity in the VCI-group.

Impact: This study applied T₂-prepared time-encoded pCASL in cerebral small vessel disease (cSVD) patients and healthy controls to study subtle BBB-damage. Although T₂-values showed no significant differences yet, the T₂-values seem to decay earlier in cSVD, suggesting earlier water-transport into tissue.

Keywords: Arterial Spin Labelling, Machine Learning/Artificial Intelligence

Motivation: Hemodynamic disturbance is one of the neuropathological characteristics of Parkinson's disease (PD). Multi-delay arterial spin labeling (m-ASL) MRI can optimize the accuracy of cerebral blood flow (CBF) quantification by taking into account arterial transit time (ATT). 

Goal(s): We aimed to comprehensively explore the detailed abnormalities of hemodynamics in PD and verify the application of m-ASL in PD diagnosis.

Approach: Voxel-based analysis and machine learning approach were applied to this study. 

Results: Our findings identified impaired hemodynamics in PD with regional abnormalities of CBF, ATT and cerebral blood volume, providing complementary depictions of perfusion disruption in PD and highlighting the clinical feasibility of m-ASL.

Impact: Our results provided complementary depictions of perfusion disruption in PD, and validated the promise of m-ASL in the investigation of underlying neurodegeneration and the clinical diagnosis of PD, providing an effective neuroimaging biomarkers for the diagnosis of neurodegenerative diseases.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Velocity selective (VS)-ASL can be of great added benefit for fMRI at ultra-high field because of its specificity and ATT-insensitivity.

Goal(s): Our goal was to show the feasibility of VS-ASL at 7T with minimal TR, which involves minimizing SAR and timing parameters within the sequence.

Approach: VS-ASL was implemented using BIR4 labeling module and compared to the robust FAIR ASL. Image quality was measured based on quantified ASL-signal and tSNR-efficiency. 

Results: Good agreement between FAIR and VSS_inv-ASL was found. VSS_inv-ASL was used to create intrinsic BGS without additional SAR. A shortest TR of 4500ms was achieved which could potentially be shorted with pTx.

Impact: We showed the feasibility of Velocity Selective (VS)-ASL at UHF and the application in fMRI. VS-ASL showed comparable but less homogeneous tSNR as FAIR. VS-ASL is of added benefit for fMRI at ultra-high field because of its specificity and ATT-insensitivity.

Keywords: Arterial Spin Labelling, Perfusion

Motivation: The high SAR burden of PCASL at 7T typically requires long TRs and short label durations, reducing SNR efficiency and perfusion measurement accuracy.

Goal(s): Our goal was to maximize the SNR efficiency of PCASL at 7T.

Approach: We optimized the PCASL B₁⁺/gradient parameters and background suppression pulses to maximize SNR efficiency (i.e., balancing labeling efficiency and SAR), and utilized VERSE and dynamic B₀ shimming to reduce SAR.

Results: Compared to optimizing the PCASL parameters for maximum labeling efficiency, our max-SNR efficiency optimized parameters increased SNR efficiency by 38% and reduced TRs by 41% in vivo.

Impact: The improved SNR efficiency of our optimized 7T PCASL parameters increases the advantages of ultra-high field perfusion measurements, enabling robust and high-SNR perfusion measurement in clinically viable scan times.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: To reduce a scan time of multi-PLD PCASL imaging using a convolutional neural network (CNN) for robust estimation of partial volume (PV)-corrected ATT and CBF maps.

Goal(s): To develop a CNN to predict PV-corrected ATT and CBF from fewer PLDs, ensuring minimal accuracy loss.

Approach: Trained and validated a CNN on multi-PLD ASL data from 48 subjects, comparing its performance with a standard method.

Results: The CNN achieved low mean average errors, suggesting reduced PLD count does not significantly affect ATT and CBF estimation accuracy.

Impact: The study’s CNN reduces MRI scan times while accurately estimating brain hemodynamic parameters, such as cerebral blood flow and arterial transit time, enhancing patient comfort and diagnostic efficiency, potentially transforming cerebrovascular disease monitoring and advancing AI integration in medical imaging.

Keywords: Arterial Spin Labelling, Perfusion

Motivation:  Standard arterial spin labeling (ASL) uses modest background-suppression to enhance SNR, which may not be optimal in reducing noise.

Goal(s): Our goal was to further improve the SNR in ASL and reliably measure the cerebral blood flow (CBF) in low-perfusion scenarios such as neonates.

Approach: We utilized an enhanced background suppression to minimize the signal from static background tissue. Complex subtraction of control/labeled signals was done to correct the magnetization sign-switching in between.

Results: Enhanced background suppression combined with complex subtraction improved the reliability of CBF measurement in both neonates and adults, particularly benefiting the quality of neonatal CBF mapping.

Impact: The improvement of SNR in ASL through enhanced background suppression coupling complex subtraction can facilitate the quality of cerebral blood flow measurement. The benefits are more pronounced in low-perfusion scenarios, such as bolstering the reliability of neonatal ASL.

Keywords: Arterial Spin Labelling, Data Processing, Arterial Spin Labelling, Analysis, Bayesian, Kinetic Modelling

Motivation: Multi-delay Arterial Spin Labelling has application across multiple patient groups, but accurate quantification remains difficult, particularly for prolonged transit times and noisy data. 

Goal(s): Compare least-squares and Bayesian-inference model fitting for perfusion estimate accuracy.

Approach: Least-squares and Bayesian-inference, specifically BASIL, pipelines were run on simulated and in-vivo ASL data with different SNR with three choices of prior/initial value for arterial transit time (ATT).  The resulting cerebral blood flow (CBF) and ATT maps were compared.

Results: ATT quantification is impacted by ATT prior/initial value in Bayesian-inference fitting more than least-squares fitting. Least-squares fitting is more susceptible to CBF overestimation at lower SNR.

Impact: MD-ASL analysis method can impact ATT accuracy. Bayesian-inference fitting is better for lower SNR data when CBF is the primary interest. Least-squares fitting is better for higher SNR data, when prior/estimate is not well known, and for accurate ATT estimation.

Keywords: Arterial Spin Labelling, Brain, Single-PLD, Multi-PLD

Motivation: Long arterial transit time (ATT) may cause underestimation of CBF in single-delay arterial spin labeling (ASL) quantification.

Goal(s): Our goal is to evaluate the accuracy and reliability between single- and multi-delay ASL acquisition.

Approach: 28 subjects underwent test-retest scans ~1 week apart. Voxel-wise and regional CBF/ATT values were quantified to evaluate the test-retest reliability. ATT values obtained from 5-PLD data were used to estimate quantification errors for CBF estimated from single-delay (PLD=2s) ASL.

Results: Overall, single-delay may cause an average of 4% to 30% of CBF underestimation in 56% regions. 5-delay is a solid solution to evaluate ATT and CBF.

Impact: While single-delay ASL results in slightly higher test-retest reliability, the underestimation of CBF may compromise the quantification accuracy. Since ATT variation is more common in elderly and patients, multi-delay ASL with model-fitting analysis is expected to outperform single-delay ASL. 

Keywords: Arterial Spin Labelling, Blood

Motivation: Quantitative T2 values of ASL spins may then inform their local microenvironment.

Goal(s): In this study, we aim to conduct a technical development to demonstrate the feasibility of measuring ASL T2 at long post-labeling-delay (PLD), at a time when the spins have fully exited the vasculature.

Approach: A protocol comprised of Pseudo-Continuous Arterial Spin Labeling (PCASL) module followed by optimized background suppression pulses and 2D multiple-spin-echo (MSE) EPI readout was used to collect T2-weighted images at different post labeling delay (PLD).

Results: We estimated T2 of ASL difference signals at long PLDs and also find age related changes in T2 values.

Impact: Our result suggests that ASL spins may be used as a reporting probe to assessment the microvascular environment of the brain in health and diseases.  

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Increased B₀ inhomogeneity along the length of brain-feeding arteries at 7 Tesla is one major issue for pseudo-continuous arterial spin labeling (PCASL), which reduces the labeling efficiency, leading to loss of perfusion signal. 

Goal(s): Our goal is to improve PCASL at 7 Tesla by specifically improving B₀ field homogeneity of the vessels within the inversion region.  

Approach: We propose a vessel-specific dynamic B₀ shimming method to optimize labeling efficiency without compromising the static shim over the imaging region. 

Results: Preliminary perfusion images indicate the superior performance of our proposed 3D dynamic shimming method over global or 2D-based correction methods.

Impact: Our proposed dynamic B₀ shimming method demonstrates strong potential in improving the robustness and effectiveness of PCASL, allowing the high sensitivity and spatial resolution of 7T ASL to be fully utilized.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Improvement of the intraoperative pseudo-continuous arterial spin labeling images for resection control in brain tumor surgery at 3T.

Goal(s): Evaluate the effect of shortening RF pulse duration and gap on the labeling efficiency of PCASL and to test it in the intraoperative setting.

Approach: A study in 10 healthy volunteers was done approximating the off-resonance effects at the labeling plane. 2 PCASL sequences were tested in 2 patients.

Results: A PCASL sequence robust to off-resonance effects is obtained by shortening RF duration and gap.

Impact: Shortening the RF duration and gap improves the PCASL labeling efficiency at high B₀ off-resonance values at the labeling plane.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: The inherent low SNR of ASL limits the accuracy of cerebral blood flow (CBF) and arterial transit time (ATT) quantification. Although a postlabeling delay weighted delay method has been proposed, its benefits are not clear and cannot be used in general delay protocols.

Goal(s): To compare multi-delay protocols and estimators.

Approach: A general weighted delay estimator was proposed. Its performance was evaluated using Monte Carlo simulations and in-vivo experiments, compared to the direct model fitting.

Results: The multi-PLD/LD protocols provided a superior estimation compared to the other protocols. The L2-norm fitting and the GWD estimator may provide improved CBF and ATT estimation, respectively.

Impact: The multi-PLD/LD protocols provided superior accuracy and precision which may provide a feasible option for quantifying the dynamic characteristics of perfusion. The L2-norm fitting and the general weighted delay method may provide improved CBF and ATT estimation, respectively.

Keywords: Perfusion, Perfusion, DSC

Motivation: Transient hypoxia-induced BOLD-DSC perfusion imaging approach can noninvasively map cerebral blood flow (CBF) and cerebral blood volume (CBV). However, the reproducibility of this technique has not been previously assessed. 

Goal(s): We aimed to determine the reproducibility of BOLD-DSC measurements within a single session and across multiple sessions.

Approach: The reproducibility of trial-wise BOLD-DSC measurements within each session was assessed for each animal during week 1, while the reproducibility of weekly BOLD-DSC measurements was evaluated across all animals from week 1 to week 4.

Results: We found that reproducibility and sensitivity of hypoxia-induced BOLD changes were consistently high in both single and multiple sessions. 

Impact: The hypoxic challenge induces highly sensitive and reproducible BOLD responses across trials within a single session and consistently across multiple sessions, enabling the longitudinal and repetitive mapping of cerebral perfusion with easily implementable whole-brain BOLD-DSC MRI in mice.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: It is challenging to evaluate the health of vasculature at the arteriole/capillary level.

Goal(s): To develop an approach to measuring a physiological parameter, arterial deceleration time (ADT), which may provide useful information at the arteriole/capillary level.

Approach: Two sets of arterial transit time (ATT) measurement using VSASL with different Vcut in labeling but the same Vcut in imaging were carried out in one subject to measure ATT and ADT.

Results: The preliminary data confirmed the ATT-insensitivity of VSASL and measured an ADT from 4cm/s to 2cm/s of less than 100 ms.

Impact: This feasibility study measured a new physiological parameter: arterial deceleration time – the time for the arterial blood to decelerate from V₁ to V₂ (V₁>V₂), which may have potential value in evaluating microvascular health and clinical applications.

Keywords: Perfusion, Arterial spin labelling, shims

Motivation: The labeling efficiency of pseudo-continuous ASL (pCASL) is reduced in the presence of large B₀ off-resonance, which makes pCASL challenging at ultra-high fields due to susceptibility-induced off-resonance. 

Goal(s): We aim to significantly reduce the labeling efficiency dependence on B₀ off-resonance of pCASL to achieve highest allowed labeling efficiency at a given labeling flip angle.

Approach: 0^th- (frequency) and 1^st-order (x,y,z) shim components were used dynamically in the duration of labeling to mitigate B₀ off-resonance without affecting imaging readout.

Results: Improved labeling efficiency was achieved, which enabled higher-resolution perfusion imaging using pCASL. Selective labeling of blood was also demonstrated possible using our approach.

Impact: Our approach provides a simple method to substantially remove the labeling-efficiency dependence on B₀ off-resonance for pCASL at 7T. This enables high-quality ASL-based perfusion imaging at ultra-high fields for study of brain function, physiology, and pathology.

Keywords: Arterial Spin Labelling, Arterial spin labelling, velocity-selective ASL, CBF

Motivation: Fourier transform velocity selective inversion (FT-VSI) ASL is sensitive to B₀/B₁⁺ inhomogeneities, which can lead to pronounced artifacts in CBF imaging. 

Goal(s): Reduce B₀/B₁⁺ sensitivity and improve performance of FT-VSI by utilizing adiabatic refocusing pulses in lieu of composite refocusing pulses. 

Approach: Adiabatic hyperbolic secant (sech) pulses with MLEV-8 phase modulation were integrated into the FT-VSI train, replacing the composite pulses. Simulations and phantom acquisitions were performed to evaluate B₀/B₁⁺sensitivity and subtraction fidelity. Human CBF data were acquired to compare image quality, tSNR, and artifacts.  

Results: Adiabatic refocusing markedly improved FT-VSI robustness to B₀/B₁⁺ inhomogeneities. CBF maps showed improved tSNR, image quality, and artifact reduction. 

Impact: A novel VSASL labeling train that uses adiabatic refocusing pulses for velocity selective inversion is introduced and found to dramatically enhance performance by improving accuracy, increasing tSNR, and reducing artifacts in human CBF imaging. 

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Planning-free random vessel-encoded ASL (rVE-ASL) greatly simplifies the vessel-selective ASL scan settings and shows great potential for vascular territorial imaging in clinical applications.  

Goal(s): To theoretically and experimentally optimize rVE-ASL to establish an efficient and reliable rVE-ASL protocol
 

Approach: Simulation and in-vivo experiments were conducted to evaluate and optimize rVE-ASL in terms of labeling efficiency, total number of encoding steps, and reliability of vascular territorial and CBF measurements.

Results: Reliable territorial mapping and CBF measurements from both ICA and VA can be achieved by optimized rVE-ASL. At least 20 encoding steps are needed to achieve reliable territorial mapping and CBF measurements in rVE-ASL.

Impact: We have theoretically and experimentally optimized rVE-ASL, which can provide reliable vascular territorial mapping and CBF quantification.  The rVE-ASL technique holds a potential to be a useful imaging tool for assessing vascular territorial alterations and collaterals in various clinical applications.

Keywords: Arterial Spin Labelling, Arterial spin labelling

Motivation: Current Fourier Transform-based velocity-selective inversion (VSI) pulses are sensitive to field inhomogeneities, leading to labeling errors or inefficiency.

Goal(s): To improve the labeling robustness and efficiency of the VSI pulses for more robust and high-SNR perfusion measurement.

Approach: A new design with 6-segment FT-VSI pulse was implemented and tested in healthy subjects using dual-module VSI labeling. 

Results: Compared with the existing VSI pulse, the new pulse significantly improved the labeling robustness against field inhomogeneities and the overall labeling efficiency, leading to >15% higher ASL signal (p<0.0002) and >20% higher temporal SNR (p<0.009).

Impact: This new VSI pulse can effectively improve the labeling robustness against field inhomogeneities, while increasing the labeling efficiency and reducing the SAR. These features are especially beneficial with dm-VSASL implementation and in ultra-high field applications for delay-insensitive ASL perfusion imaging.

Keywords: Relaxometry, Quantitative Imaging, Relaxometry, MR-STAT, Clinical

Motivation:  This is the first work assessing quantitative values (T₁ and T₂) from Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) as a fast relaxometry technique in clinical setting. 

Goal(s): To assess MR-STAT as viable option for fast relaxometry in the clinic. 

Approach: We applied MR-STAT to investigate the quantitative T₁ and T₂ values of brain tissue at 3T in a heterogeneous cohort of 50 subjects (10 healthy volunteers, mixed-pathology 40 patients). 

Results: Quantitative values in normal appearing brain tissue were comparable to earlier literature. Furthermore, individual case examples (glioma, multiple sclerosis) confirmed the ability to discern pathological tissue in T₁ and T₂ values. 

Impact: Voxel values in clinical MRI are subjective. Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) quickly quantifies MR tissue properties and gives voxels quantitative values. This work demonstrates MR-STAT as fast relaxometry technique in a clinical population and assesses quantitative values.  

Keywords: Relaxometry, Modelling, Microstructure, Nervous System

Motivation: T₁ estimations using the MP2RAGE methodology are biased by Magnetization Transfer (MT) effects. A quantitative MT-based solution was previously proposed in which the inversion efficiency of the preparation pulse (Q) was fixed; we sought to alleviate this strong hypothesis.

Goal(s): To better understand the influence of free water T₂ (T_2,f) on Q in the scope of MP2RAGE-T₁ brain mapping.

Approach: A better modeling of the MP2RAGE involving a discretized preparation pulse is employed, and tested for fixed and free T_2,f values.

Results: The T₁ bias is highly dependent on the T_2,f values, calling for a better and accurate estimation of this parameter.

Impact: Quantitative MT-derived T₁ estimation in the MP2RAGE methodology remains dependent on the estimated free water T₂ values because of its impact on the inversion efficiency pulse.

Keywords: Relaxometry, Quantitative Imaging, Toxicity; Radiotherapy; Biomarker; Head and Neck

Motivation: Due to limited options for early monitoring and interventions, radiation therapy (RT) for head and neck cancer patients often leads to dysphagia following treatment due to fibrosis development in swallowing muscles.

Goal(s): The goal of this work is to report findings from a retrospective cohort who received RT treatment and longitudinal T1/T2 map imaging. 

Approach: Evaluating at pre-, mid-, post-, and late- RT allows for statistical analysis of changes in median T1/T2 values.

Results: Our hypothesis was confirmed that kinetics are discernable for T1 only, but limited correlation to dose and objective measures of muscle damage was seen in various structures.

Impact: At present, there exists no option for the early monitoring of injury from radiation therapy of swallowing muscles related to dysphagia. The aim of this work is to investigate Quantitative MR Relaxometry as a method to monitor for iatrogenic injury.

Keywords: Multi-Contrast, Quantitative Imaging, bSSFP, brain, T1, T2, Relaxometry, field inhomogeneity, proton density

Motivation: Addressing the need for simplified, time-efficient, and unbiased quantitative imaging in human brain.

Goal(s): Evaluating novel analytical method, ORACLE, to simultaneously quantify T1, T2, proton density (PD), and magnetic field inhomogeneity (B0) in human brain based on balanced steady-state free precession (bSSFP) profiles.

Approach: Acquiring bSSFP data for simultaneous multi-parameter quantification and reference multi-echo spin-echo, MP2RAGE and dual-echo gradient-echo data in 4 human subjects.

Results: Quantifications using bSSFP profiles and ORACLE was consistent with reference methods, although magnetization transfer effects led to a 15% consistent underestimation of T1. Proposed method has faster acquisition and parametric estimation comparing to other methods combined.

Impact: This novel analytical time-efficient method extracts a wide range of quantitative parameters from bSSFP profiles, which can be a valuable alternative to existing reference methods, multi-echo spin-echo, MP2RAGE and dual-echo gradient-echo, that quantify one parameter at a time.

Keywords: Relaxometry, Body

Motivation: The acquisition time of volumetric relaxometry techniques is constrained by the sampling efficiency and confounding factors such as fat or the B1 inhomogeneity.

Goal(s): To develop a method for volumetric T1- and T2-mapping that improves efficiency while accounting for confounding factors.

Approach: A Cartesian acquisition with spiral profile ordering is employed to increase sampling efficiency. A subspace reconstruction is proposed to perform B1- and water-specific T1- and T2-mapping considering the exact k-space sampling pattern.

Results: Simulation, phantom and in-vivo experiments were performed to evaluate the proposed method with regard to its quantification performance and its B1 sensitivity at 3T.

Impact: Subspace reconstruction in combination with a CASPR trajectory can improve the scan's efficiency and sampling flexibility while correcting for confounders such as fat or B1. The technique may be valuable to develop volumetric relaxometry in clinically acceptable scan times.

Keywords: Relaxometry, Relaxometry, Ultra-high field; 7T; R2*; high resolution; deep gray mattern; subcortical

Motivation: While conventional 7T systems provide increased SNR, their gradient systems lack the performance to acquire high-resolution GRE data with very fast sampling/many echoes.

Goal(s): To leverage a 7T with high-performance gradients to acquire more echoes than on conventional 7T systems and assess the potential for high-resolution R2* mapping.

Approach: Multi-echo GRE data with varying number of echoes was acquired at a 7T Terra.X Impulse Edition and 7T Plus. Conventional logarithmic-linear and advanced stretched exponential fits were performed.

Results: Sampling more echoes enables fitting advanced models which yield lower R2* standard deviation and root-mean-squared-errors.

Impact: Combining 7T with high-performance gradients enables high spatial and temporal resolution multi-echo GRE data. Hence, R2* mapping can be performed with novel multi-parametric fits, enabling new avenues in biophysical modeling as well as signal denoising and decomposition algorithms.

Keywords: Relaxometry, Multi-Contrast, Myelin Water Imaging

Motivation: Multi-echo gradient-echo (mGRE) MRI enabled non-invasive quantification of myelin water fraction (MWF) of the human brain.

Goal(s): The MWF may depend on field strength that changes the T₂^* decay and the results need to be verified by histological staining.
 

Approach: We performed mGRE-based MWF on in-vivo and ex-vivo human brain at high resolution and revealed the accuracy of the measurements using histological staining at both 3T and 7T.

Results: The MWF-derived from 7T was systematically higher than those from 3T and the in-vivo and ex-vivo measurements showed good agreement. The MWF at 3T and 7T both demonstrated good correlations with myelin basic protein.

Impact: These findings indicated the MWF mapping could reliably depict the myelin content in the human brain, although the measurement were field-strength dependent.

Keywords: Relaxometry, Contrast Mechanisms, Spin Lock

Motivation: Composite metric R2-R1rho (1/T2–1/T1rho) could be utilized for probing chemical exchange.. However, a persistent challenge lies in the confounding influences of magnetization transfer (MT) effects on R2, which was not fully discussed in literatures.

Goal(s): In this study, we reported our investigation on this effect and proposed an acquisition strategy to improve the specificity of the composite metric (R2-R1rho) to thethe chemical exchange effect.

Approach: We demonstrated our findings and the proposed method using simulation, phantom, and in vivo experiments.

Results: From our preliminary results, composite metric (R2-R1rho) to detect chemical exchange without the influence from magnetization transfer effect.

Impact: Using improved composite metric (R2-R1rho) to detect chemical exchange without the influence from magnetization transfer effect.

Keywords: Relaxometry, Relaxometry, T2 Mapping, T2* Mapping

Motivation:  T₂ and T₂* mapping can quantitatively characterize tissue pathologies, improving diagnosis and treatment, but their clinical applications are hindered by relatively long scan times.

Goal(s): To develop an ultrafast method for simultaneously obtaining T₂ and T₂* mapping.

Approach: A biaxial spatiotemporally encoded (SPEN) sequence with multi-spin-echo trains and spiral out-in-out-in trajectory was developed to obtain multiple images with different echo times within a single shot. The acquired signal was fitted to yield simultaneous T₂ and T₂* mapping.

Results: Numerical simulations and in vivo rat brain and kidney experiments were conducted to validate the proposed method.

Impact: We developed an ultrafast technique to simultaneously obtain T₂ and T₂* mapping in 150 ms, potentially facilitating the use of T₂ and T₂* mapping in scenarios requiring high time resolution.

Keywords: Relaxometry, MR Fingerprinting

Motivation: T₁ and T₂ accuracy in the brain is difficult to assess, since there is no ground truth available.

Goal(s): To investigate how well relaxometry methods agree.

Approach: We compare Magnetic Resonance Fingerprinting (MRF) T₁ and T₂ mapping with Variable Flip Angle (VFA) T₁ mapping and Multi-Echo Spin Echo (T₂) mapping in 11 anatomical brain regions for 10 healthy volunteers, and in the relevant spheres of the NIST phantom.

Results: MRF underestimates T₁ and T₂ in comparison with T₁ VFA and T₂ MESE in the human brain, especially in myelin-dense areas. Less T₁ and no T₂ bias is present in the NIST phantom.

Impact: Quantitative T₁ and T₂ relaxometry techniques are more consistent in the NIST phantom than the human brain. Deviations could be caused by magnetisation transfer, whose impact on T₁ and T₂ relaxation mechanisms needs further investigation. 

Keywords: Relaxometry, Validation, Histology, Myelin, Iron, In vivo vs ex vivo, Fixation

Motivation: Estimating myelin and iron concentration maps from in-vivo MRI yields biased estimates because MR-to-microstructure linear mappings are derived from fixed-postmortem human brain tissue.

Goal(s): We assessed whether taking into account the changes of relaxation rates from in-vivo to hydrated fixed ex-vivo specimens would allow the use of current MR-to-microstructure linear mappings for in-vivo MRI.

Approach: We introduced a pipeline that accounts for the major relaxation-rate changes during fixation and hydration, and compared the estimated MRI-based myelin parameters to their counterparts from light microscopy in the human corpus callosum.

Results: We found that including these changes significantly improved the accuracy of the myelin estimates.

Impact: We proposed a new method that significantly improves the MRI-based myelin and iron maps estimation from in-vivo longitudinal and effective transverse relaxation rates.

Keywords: Relaxometry, White Matter

Motivation: There remains a gap in knowledge surrounding what microstructural features impact similar myelin qMRI metrics.

Goal(s): The goal of this work is to evaluate the relationship between a novel axon diameter surrogate and myelin qMRI metrics.

Approach: Ex vivo ferret spinal cords were imaged at 15T using multiple spin echo, selective inversion recovery and diffusion tensor imaging sequences.

Results: BPF was found to have a negative correlation with the axon diameter surrogate measure. MET₂ derived metrics were found to have no correlation with the axon diameter surrogate measure. 

Impact: The diffusion time dependence of the radial diffusivity is thought to report on axon diameter towards detecting microstructural changes as a result of pathology. This work provides further evaluation of this metric and other relaxation parameters of white matter. 

Keywords: Relaxometry, Relaxometry, MR-STAT, Multiple sclerosis, Machine Learning

Motivation: Radiology workflow around multiple sclerosis (MS) patients is time-consuming. 

Goal(s): To automatically count and measure individual white matter anomalies in MS patients from a five-minute Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) scan. 

Approach: We imaged ten healthy volunteers (HV) and six MS patients using a five-minute MR-STAT protocol. Resulting quantitative data from seven HVs was fit to a multivariate Gaussian probabilistic model. The model was tested on three HVs and six MS patients. 

Results: Automatic anomaly detection was moderately accurate in MS patients. No anomalies were found in HVs. These results underline the potential for a shorter acquisition with automatic outlier detection. 

Impact: MRI protocols for MS patients are lengthy and the assessing the images is a time-consuming task for the radiologist. We combine a fast (five-minute) MR-STAT relaxometry scan with a data-driven, automatic outlier detection strategy to potentially accelerate the clinical workflow.

Keywords: Relaxometry, Spinal Cord

Motivation: In spinal cord T₂* relaxometry, only mono-exponential models have previously been used, neglecting the potential presence of multiple compartments.   

Goal(s): Determine if a mono- or bi-exponential model is better for T₂* relaxometry in the cervical spinal cord white matter (WM) and grey matter (GM).

Approach: Mask the ventral half of the GM and WM in a 7-echoes GRE acquisition. Fit a mono-/bi-exponential model to the average signal in the masks for each slice. Compute R², F-tests and p-values.

Results: A bi-exponential model gave statistically better results in WM. No relevant difference between the models was measured in GM for most slices.

Impact: A bi-exponential model is statistically better than a mono-exponential one for T₂* relaxometry in spinal cord white matter, but not grey matter. The model can be used for contrast optimization, e.g. to improve lesion detection in demyelinating diseases.

Keywords: Relaxometry, Spectroscopy, Downfield

Motivation: NAD⁺ is a key metabolite in aging and disease, but its absolute in vivo tissue quantification requires correction for T₁ and T₂ relaxation effects.

Goal(s): Our goal was to determine T₁ and T₂ of NAD⁺ in human brain in vivo at 7T.

Approach: We utilized spectrally-selective downfield spectroscopy with slice localization.

Results: We measured an average T₁ of 164.6±28.1ms and an average T₂ of 33.5±10.3ms across three NAD⁺ downfield resonances.

Impact: Our measurements of NAD⁺ T₁ and T₂ in human brain can be used as correction factors to quantify absolute concentration of NAD⁺, a potential biomarker to study metabolic derangements in many diseases.

Keywords: Relaxometry, Relaxometry, Low-Field MRI

Motivation: Quantitative magnetic resonance imaging can provide novel insights into the brain’s tissue microstructure, however, such methods have limited availability at ultra-low field. 

Goal(s): To develop DESPOT1 approach at ultra-low field.

Approach: We acquired spoiled gradient recalled echo images across multiple flip angles at low field (64 mT) and fit the signal to estimate T1 using the DESPOT1 framework.

Results: While challenged by limited SNR at low field, our results demonstrate the feasibility to measure T1 at low field from multiple flip angle images. Through additional optimization, such methods may allow low field systems to provide sensitive measures of brain tissue microstructure.  

Impact: Our results demonstrate the ability to perform T1 relaxation time mapping via DESPOT1 at ultra-low field for the first time. Improvements in the described approach could enable  sensitive measurements of brain microstructure at ultra-low field.

Keywords: Susceptibility/QSM, Susceptibility, Fat/Water Separation

Motivation: Gradient echo imaging using in-phase echoes has been proposed to simplify the fieldmap estimation in water–fat regions. The use of so-called effective multi-peak in-phase echo times allow for the bias-free QSM estimation in body regions in the presence of complex fat-models. Conventionally, the in-phase paradigm rigidly constrains the selection of echo times, often balancing acquisition speed, resolution, and SNR against one another. 

Goal(s): .

Approach: .

Results: This study demonstrates the feasibility of a nearly unrestricted selection of the first echo time, without introducing significant quantification bias. This advance allows for a more flexible and efficient imaging process.

Impact: This work introduces a simple, flexible and bias-free body QSM acquisition strategy based on so-called pseudo in-phase echos that allows for considerably faster acquisitions while simultaneously increasing the SNR efficiancy

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Total Field Inversion, Boundary Element method, Fast Multipole method

Motivation: The study aims to improve quantitative susceptibility mapping (QSM) precision at region of interest (ROI) boundaries where background field interference affects accuracy.

Goal(s): To introduce a novel boundary element method total field inversion (BEM-TFI) enhanced by the fast multipole method (FMM) for high-resolution QSM.

Approach: A comparative assessment of BEM-TFI technique was performed with traditional QSM methods, utilizing in-vivo data and simulated field maps to determine inversion quality and background field removal efficiency.

Results: Enhanced by FMM, the BEM-TFI method demonstrated significant improvements in accurately discerning tissue susceptibility from background noise, indicating a substantial advancement in the outcomes of QSM.

Impact: The BEM-TFI enhancement in QSM accuracy allows for more detailed characterization of the brain's cortex, potentially enriching neuroscientific research and elevating the quality of neuroimaging data.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Orientation-Adaptive, Latent Feature Editing, OA-iQSM

Motivation: The performances of most DL-QSM methods are limited to MRI phase data of pure-axial acquisition orientation. 

Goal(s): In this work, we would like to propose a novel DL-based end-to-end neural network for QSM reconstruction from phase data of arbitrary dipole orientations. 

Approach:  A novel Latent Feature Editing (LFE) module to learn the encoding of acquisition orientation vectors and seamlessly integrate them into the latent features of deep networks to make them orientation-adaptive. 

Results: Both simulated and in vivo experiments demonstrate that the proposed LFE module can result in desirable QSM images at arbitrary oblique head orientations. 

Impact: This work introduces a new DL paradigm, allowing researchers to develop innovative QSM methods without requiring a complete overhaul of their existing architectures.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Source Separation, DECOMPOSE, Multi-echo

Motivation: DECOMPOSE-QSM is a susceptibility source separation method that has the potential for many clinical applications. However, its sensitivity to input QSM acquisition parameters and reconstruction method, and its repeatability are unknown.

Goal(s): To investigate the performance and repeatability of DECOMPOSE-QSM with QSM calculated using various acquisition schemes and multiple dipole inversion methods.

Approach: Eight different QSM dipole-inversion methods were used as inputs for DECOMPOSE-QSM. Multi-echo GRE were acquired with different protocols to evaluate reproducibility and sensitivity to the acquisition.

Results: We reduced susceptibility contrast differences from different QSM methods by normalizing input susceptibilities. DECOMPOSE-QSM results were repeatable across different subjects.

Impact: We showed that, with normalization, inputting QSM from different inversion methods yields similar DECOMPOSE-QSM separation maps and that this technique is reproducible. Taking into account its sensitivity to different acquisition parameters will facilitate further clinical applications of DECOMPOSE-QSM.

Keywords: Data Processing, Aging

Motivation: Studies have demonstrated that iron accumulation rates in various gray matter nuclei are different throughout an individual’s lifetime, yet no study has quantitatively evaluated how the spatial distribution of brain iron might evolve with normal physiological development and aging.

Goal(s): This study was to investigate the change trajectories of spatially distribution of iron in the deep gray matter nuclei as a function of ageing using QSM. 

Approach: 3D texture analyses were performed on QSM maps to calculate the texture features using the GLCM.

Results: The quadratic regression results characterized differential age-dependent trajectories of texture features in gray matter of basal ganglia, midbrain and cerebellum. 

Impact: Quantitatively evaluated the spatial distribution properties of brain iron during lifespan might provide critical information for understand the brain development and aging, as well as predicting cognitive or neurodegenerative diseases.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Cortex orientation, Myelin concentration

Motivation: Effect of cortex orientation relative to the magnetic field can impede quantitative susceptibility mapping (QSM) from being established as a robust measurement of cortical pathology.

Goal(s): To identify the significance of cortical orientation effect in QSM and its underlying contribution from cortical myelin.

Approach: QSM was performed in eight healthy subjects at isotropic 0.75mm resolution at 3T. The relationship between QSM and cortical orientation was evaluated in cortical regions across the brain. The region-specific effect strength was correlated with region-average myelin approximation.

Results: Significant orientation effect was observed in most brain regions, including significant correlation between the region-specific effect strength and myelin estimation.

Impact: This study represents an initial effort to uncover the cortex orientation effect in cortical grey matter QSM result towards establishing QSM as a robust clinical tool for cortical pathology.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Vessels, Artifacts

Motivation: χ-separation is an advanced QSM method that provides para- and diamagnetic susceptibility maps. Despite its potential utilities, both maps reveal (erroneously) high intensity signals from vessels, hampering their applications and quantification. 

Goal(s): Proposing a vessel segmentation method designed for χ-separation by utilizing physical properties of vessel signals in χ-separation.  

Approach: Acquiring seeds by informing physics of vessels in χ-separation, and vessel geometry characteristics guided-region growing is implemented to generate vessel masks.

Results: Our method successfully creates vessel masks for both susceptibility maps and demonstrates to be robust to various input types. When applied to an ROI analysis, reduced variability in measurements was shown.

Impact: The novel vessel segmentation method utilizes physical properties of vessels in χ-separation for reliable and robust segmentation, providing substantially improved segmentation results. It may help us to improve downstream analysis when quantifying susceptibility of myelin or tissue iron excluding vessels.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, subvoxel QSM

Motivation: Subvoxel QSM could be beneficial for assessing the knee cartilage but requires two separate sequences for reconstruction by using APART-QSM.

Goal(s): To achieve subvoxel QSM reconstruction of knee cartilage in a single scan. 

Approach: A multi-contrast framework was used to simultaneously estimate $$$T_1$$$, $$$T_2$$$ and $$$T_2^{*}$$$ mapping in one scan. The magnitude and phase images were generated based on the signal equation. The preprocessed phase and $$$R_2^{'}$$$(=$$$1/{T_2^*}$$$-$$$1/{T_2}$$$) were used for subvoxel QSM reconstruction. The results were compared with conventional approach using two sequences (GRE+MSE). 

Results: The subvoxel QSM results using the multi-contrast framework have good agreement with the conventional condition. 

Impact: The diamagnetic and paramagnetic susceptibility source separation of the knee cartilage could be achieved in a single scan using a multi-contrast framework. This technique can provide specific information to assess the tissue magnetic properties of the knee cartilage.

Keywords: Gray Matter, Quantitative Susceptibility mapping

Motivation: MRI signals have phase information from the GRE sequence, which reflects B0 field homogeneities. 

Goal(s):  Due to acquisition, the phase is converted from complex data, ranging from -π to π and causing visual discontinuities. However, previous learning-based approaches have difficulties processing 3D brain data directly. 

Approach: In this study, we introduced an unsupervised refinement based on Deep Image Prior to enhance the performance of the pre-trained networks (PHU-DIP), and the inference were performed on one simulated and one in vivo brain. 

Results: The PHU-DIP method corrected the misclassification regions from the pre-trained networks and exhibited the significant time-efficiency compared to conventional method.

Impact: The PHU-DIP provided a refinement scheme that help to improve the performance of a well-trained network. This technique could also be expanded onto other training modes and other pathological conditions. 

Keywords: Susceptibility/QSM, Susceptibility, High-resolution anatomy

Motivation: High-resolution χ-separation at 7T can delineate detailed structures related to iron and myelin concentrations in the brain. However, it has the challenge of requiring an R2 map, which is not practical at 7T due to SAR and scan time. 

Goal(s): Our objective is to generate high-resolution χ-separation maps at 7T.

Approach: An R2* 7T-to-3T conversion network to transform a 7T R2* map into its 3T counterpart is developed. Then, 𝜒-separation is processed via QSMnet, χ-sepnet-R2*, and resolution generalization.

Results: We successfully produced high-quality and high-resolution 𝜒-separation maps only from multi-echo gradient echo data at 7T.

Impact: This study suggests a solution for the technical challenge of requiring R2 map in 7T χ-separation, enabling high-resolution (=650 um) χ-separation. This may benefit the analysis of iron and myelin concentration changes in various neurodegenerative diseases through detailed structural examination.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping

Motivation: Quantitative Susceptibility Mapping (QSM) at 7-Tesla (7T) has been implicated to improve assessment of neurodegenerative disorders but has yet to be integrated into clinical practice.

Goal(s): We aimed to address the growing demand for a standardized and optimized QSM reconstruction protocol that enables accurate quantification of susceptibility, mitigates contaminating artifacts, and is clinically feasible. 

Approach: Here, we compared 32 end-to-end QSM processing pipelines and evaluated their performance.

Results: We show that reconstruction with Laplacian phase-unwrapping, RESHARP background field removal, and MEDI dipole inversion outperformed other pipelines in suppressing artifacts.

Impact: Our optimized pipeline results in a 7T QSM reconstruction with clear cortical and subcortical boundaries, and mitigates susceptibility artifacts. Furthermore, the comprehensive review of QSM processing algorithms highlights Laplacian, RESHARP, and MEDI as robust algorithms with reliable, consistent performance.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, cognitive decline

Motivation: Brain iron content may play an important role in the development of Mild Cognitive Impairment (MCI) and dementia due to Alzheimer’s Disease (AD).

Goal(s): To investigate the utility of baseline brain iron levels, measured by quantitative susceptibility mapping (QSM), to predict time to onset of symptoms of MCI and global cognitive decline among older adults with normal cognition at baseline.

Approach: Cox regression models and linear mixed models were used.

Results: Higher brain iron levels in entorhinal cortex and putamen were associated with an earlier time to MCI onset and greater global cognitive decline, independent of the volume and amyloid of those regions.

Impact: Brain iron deposition assessed by QSM MRI may help predict risk of MCI onset and cognitive decline among cognitively normal individuals.

Keywords: Susceptibility/QSM, Susceptibility, Gray Matter/ Ex-Vivo Applications

Motivation:  Previous studies have demonstrated the correlations between iron and paramagnetic susceptibility and myelin and diamagnetic susceptibility. However, there has yet to be a quantitative layer-wise comparison with histology.

Goal(s):  Our objective is to validate laminar structures of χ-separation against histology in V1.

Approach:  In V1, we performed laminar profiling of χ-separation, iron-, and myelin histology. The profile was obtained by sampling points at 5% intervals along the cortical depth, oriented perpendicularly to the cortex.

Results: The cortical depth profile reveals that both χ_para with iron histology and χ_dia with myelin staining exhibit similar profiles and peaks at the location of the Gennari line.

Impact: By comparing the cortical depth profile in the V1 region including the location of the Gennari line between χ-separation and histology, we have confirmed that χ-separation (χ_para, χ_dia) accurately represents the quantitative amounts of iron and myelin with precision.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping

Motivation: White matter (WM) microstructure can affect estimation of WM susceptibility with QSM. However, as QSM fits all voxels at once, it is less understood how it affects estimation of surrounding tissue.

Goal(s): Our goal is to demonstrate the effect of a cylindrical microstructure on surrounding tissue in a digital phantom.

Approach: We synthesize a digital phantom with parallel rods surrounded by a rim with random dots. We estimate susceptibility with (QSM+) and without (QSM) account of microstructure.

Results: QSM is biased inside the rim, and this error spreads to the surrounding tissue characterized by a power law. QSM+ improved susceptibility fitting.

Impact: It may be important to account for microstructure in WM even though one may only be interested in analyzing surrounding tissue like gray matter. Failing to do so could lead to misinterpretation of tissue magnetic susceptibility.

Keywords: Susceptibility/QSM, Electromagnetic Tissue Properties

Motivation: While high-resolution quantitative susceptibility mapping (QSM) reveals unprecedented anatomical cytoarchitectures, delineation of certain substructures may be limited in regions containing both iron and myelin.

Goal(s): To demonstrate iron and myelin-specific anatomy inside human brain using sub-millimeter susceptibility source-separation (chi-separation).

Approach: Sub-millimeter multi-orientation QSM and chi-separation were obtained on postmortem human hemibrain at 7T. Capabilities of QSM, χ_para and χ_dia contrasts for delineating neuroanatomy were compared.

Results: While iron-rich substructures like line of Gennari can be readily identified in QSM, χ_dia helps reveal small fibers including striatal tracts, perforant pathway and fibers in cortical/subthalamic area.

Impact: Sub-millimeter susceptibility source separation images can delineate neuroanatomical substructures in the human brain with increasing specificity to iron or myelin related cytoarchitecture.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Susceptibility source separation, R2* mapping, Artifact correction, Iron imaging, Myelin imaging

Motivation: An advanced quantitative susceptibility mapping (QSM) technique, χ-separation, requires tissue field map and R₂* to separate paramagnetic and diamagnetic components. As the background field is removed to acquire the tissue field map, the background R₂* needs to be removed to accurately estimate paramagnetic and diamagnetic susceptibility maps.

Goal(s): Investigate the effect of background R₂* correction on χ-separation.

Approach: The effect of background R₂* correction on χ-separation was tested by varying the background R₂* with multiple head orientations and k-space filtering.

Results: Background R₂* correction successfully reduced overestimation in χ-separation maps in different head orientations and low-pass filtering levels.

Impact: Background R₂* correction enables consistent χ-separation across different head orientations and k-space filtering.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Breast

Motivation: Quantitative susceptibility mapping (QSM) has recently been used to detect breast microcalcifications (MCs) which could be the precursor lesions to breast-carcinoma. However, acquiring high-resolution (HR) QSM maps reduces the signal-to-noise ratio (SNR), making detection of MCs challenging.

Goal(s): Improve the SNR in HR-QSM for better MCs visualization using deep-learning-based denoising.

Approach: A complex-valued bias-free CNN (CV-BFCNN), adapted from real-valued BFCNN, was trained on complex-valued MR data with Gaussian noise to denoise multi-echo gradient-echo images used for QSM processing.

Results: CV-BFCNN improves SNR in HR-QSM and processes complex-valued MR data directly when compared to real-valued BFCNN, and allows enhanced visualisation and detection of MCs.

Impact: The application of complex-valued deep-learning-based denoising in high-resolution QSM has substantially improved SNR and detection of micro-calcifications, a precursor to breast cancer. This helps QSM, an ionizing radiation-free alternative in detection and visualization of microcalcifications in the breast.

Keywords: Susceptibility/QSM, Data Analysis

Motivation: Magnetic susceptibility in MRI offers non-invasive insights into brain substances like iron and myelin, affecting brain function and disease. The χ-separation method promises to enhance these insights by better estimating substance concentrations.

Goal(s): To assess the test-retest reproducibility of χ-separation methods to ensure their reliability for wider use in both research and clinical settings.

Approach: Reproducibility was tested by repeating scans using 3T MRI. Statistical analysis by Bland-Altman, regression, and ICC were used for evaluation.

Results: χ-separation demonstrated high reproducibility for both positive and negative susceptibility map analyses compared to previous study regarding QSM 

Impact: This study affirms the robustness of χ-separation in MRI, enhancing the detection of iron and myelin concentrations and paving the way for more accurate brain pathology studies, potentially revolutionizing both clinical diagnostics and research into neurodegenerative diseases.

Keywords: Susceptibility/QSM, Susceptibility, Susceptibility Tensor Imaging

Motivation: When solving the Susceptibility Tensor Imaging problem, fast algorithms based on Least Squares require an elevated number of acquisitions, while more robust solvers that use DTI information may produce over-smoothed solutions. 

Goal(s): To create a deep neural network based reconstruction algorithm to produce high SNR STI images with a reduced number of MRI acquisitions.

Approach: Use a physics-informed deep neural network approach, trained with various geometrical objects, capable of accurately reconstructing susceptibility tensors.

Results: We obtained susceptibility tensors with the expected anisotropy, better alignment with DTI eigenvectors and high SNR. 

Impact: Our STI-net algorithm is capable of reconstructing accurate STI images with higher SNR, compared with traditional algorithms.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, functional Quantitative Susceptibility Mapping

Motivation: fQSM quantitative and spatially-specific information on brain activity may be valuable in studying cortical substructures. However, fQSM response to varying stimulus intensity is unknown, and, as for QSM, reduced z-coverage may affect quantification.

Goal(s): We aimed to assess fQSM linearity to stimulus intensity and its dependence on z-coverage.

Approach: We employed visual stimuli with different contrasts and acquired whole-brain fQSM datasets that were truncated to simulate partial coverage.

Results: We reported fQSM response linearity to different contrasts and, while extremely small coverage led to brain activity underestimation, whole-brain acquisitions were not necessary to obtain accurate results.

Impact: Linearity and feasibility at reduced z-coverage, together with high spatial specificity, suggest that fQSM may provide added value to the functional study of cortical substructures.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping

Motivation: While GRE and SWI are the primary methods for identifying iron deposition in cerebral cavernous malformation (CCM), improved preclinical lesion characterization can be achieved by using Quantitative Susceptibility Mapping (QSM).

Goal(s): Our goal was to introduce the use of QSM in a preclinical CCM model and evaluate the impact of the different QSM methods available.

Approach: 8 healthy mice and 13 CCM mice were scanned using a multi-gradient echo and images were processed through each QSM method then compared using RMSE. 

Results: Each QSM method displayed large susceptibilities in areas suspected of CCM lesions.  

Impact: The addition of QSM for preclinical CCM may benefit longitudinal analysis. By establishing the use of QSM and further development in QSM calibration with ex vivo studies, QSM can be used for tracking CCM lesion progression noninvasively. 

Keywords: Susceptibility/QSM, Head & Neck/ENT

Motivation: Identifying hypoxia in head and neck squamous cell carcinoma (HNSCC) could improve treatment. Quantitative susceptibility mapping (QSM) offers a potential method for measuring tissue composition and oxygenation.

Goal(s): To develop a robust, repeatable pipeline for QSM in the head and neck region.

Approach: We tested various QSM reconstruction pipelines and compared their intra- and inter-session repeatability, before applying an optimized pipeline to a HNSCC patient dataset.

Results: A pipeline using ROMEO phase unwrapping, V-SHARP background field removal, and iterative Tikhonov susceptibility calculation was found to be more repeatable than the previously reported best pipeline and showed nodal susceptibility differences in a HNSCC patient.

Impact: This new optimized pipeline provides repeatable susceptibility values in key ROIs through the head and neck region and detected nodal susceptibility differences in a HNSCC patient. Therefore, it is applicable for clinical studies of tissue susceptibility and oxygenation in HNSCC.

Keywords: Susceptibility/QSM, Artifacts, chi-separation

Motivation: In QSM and χ-separation (chi-separation), artifacts from various sources may be introduced. The oversight of these artifacts could lead researchers to analyse inaccurate maps, resulting in potentially erroneous conclusions. 

Goal(s): The primary objective of this research is to investigate the characteristics, origins, and solutions related to artifacts encountered in QSM and χ-separation.

Approach: We processed QSM and χ-separation in 364 subjects from Parkinson’s disease, Alzheimer’s disease, hypertension, and alcohol-exposed adolescents development studies, reporting various types of artifacts. They are categorized and explored for origins and potential solutions.

Results: This study identified and provided solutions for 11 artifact types.

Impact: While processing QSM and χ-separation in diverse subjects and vendors, various artifacts emerged. This study categorized these artifacts, investigated origins, mitigation strategies, and discernible effects on QSM and χ-separation results, aiding researchers and practitioners in artifact identification, correction, and exclusion.

Keywords: Susceptibility/QSM, Susceptibility, Dynamic Susceptibility Contrast MRI, Cellular Structures, Tissue Structures, Simulation

Motivation: Dynamic susceptibility contrast (DSC) MRI is a robust method for imaging brain tumors, and there is potential to glean more clinically useful data than is obtained with standard-of-care DSC-MRI.

Goal(s): We aimed to systematically investigate the effect of varied cellular features on the difference in DSC-MRI-derived ΔR₂* time curves to evaluate the feasibility of recovering these features in real tissue.

Approach: We generated 3D tissue structures of ellipsoids (determined by specified parameters and randomly distributed) and applied the finite difference finite perturber method to compute ΔR₂*.

Results: In general, ΔR₂* increased then plateaued as cell volume fraction, aspect ratio, and size increased.

Impact: We simulated T₂*-weighted DSC-MRI signal for 3D tissue structures with varied cellular features to evaluate the feasibility of recovering these features in real tissue. Results suggested that cell volume fraction, aspect ratio, and size may be identifiable biomarkers.

Keywords: Susceptibility/QSM, Quantitative Imaging, Hypoxia, High-Field MRI

Motivation: Investigating R₂* and QSM for deoxyhemoglobin detection is vital for diagnosing and understanding diseases where tissue oxygenation is frequently compromised.

Goal(s): To evaluate R₂* against QSM for their ability to detect deoxyhemoglobin changes in a controlled hypoxic environment using a mouse model.

Approach: Employ a graded hypoxia protocol in naïve, female C57Bl/6 mice, capturing 3D MGE images at various oxygen levels (30%, 15% and 10%) to measure R₂* and QSM responses.

Results: R₂* demonstrated significant sensitivity to hypoxia in brain regions, particularly the hippocampus, unlike QSM, suggesting its potential as a superior hypoxia biomarker.

Impact: This study reveals R₂* relaxometry's superior sensitivity to the detection of changes in deoxyhemoglobin over QSM, potentially improving early detection and monitoring of hypoxia-related diseases, such as Multiple Sclerosis, and informing future clinical imaging protocols.

Keywords: Electromagnetic Tissue Properties, Ex-Vivo Applications, Genetic Diseases, Neurodegeneration, Iron

Motivation: Ex-vivo histology is the most common method to assess iron accumulation in frontotemporal lobar degeneration, but in vivo assessment is crucial to unravel disease mechanisms.

Goal(s): This study aims to assess the distribution and severity of iron accumulation post-mortem using susceptibility MRI and compare this to histological data.

Approach: We analyzed postmortem tissue of 5 MAPT-FTLD and 2 C9orf72-FTLD cases using a histological iron staining, T2*-weighted MRI, and QSM maps.

Results: We found that histology, susceptibility MRI, and QSM show good correspondence of iron distribution in FTLD brain tissue. However, sharp details are better seen on T2*-weighted MRI, and U-fibers on QSM maps.

Impact: Our study showed that susceptibility-based imaging can be used to visualize iron accumulation in FTLD; with T2*-weighted MRI and QSM showing complementary spatial information. Therefore, these two methods should be used parallel and not independent of each other.

Keywords: Susceptibility/QSM, Susceptibility, Clinical,Statistics,Referencing

Motivation: In QSM, there is no well-established susceptibility baseline . This can be determined a-posteriori by referencing to a specific tissue but this may impact statistics in clinical studies.

Goal(s): To derive an expression for a t-test under referencing, and to investigate the effect of commonly used reference regions on a temporal lobe epilepsy study.

Approach: Reference regions were compared: three anatomical structures and three derived from global thresholds. Changes in covariances, t-test results, and regional susceptibility distributions are presented.

Results: Referencing to small regions has a bigger impact on statistical analyses than large references. Reference regions should have a low variance across groups.

Impact: Referencing QSM susceptibility values is essential, but highly contested in practice, particularly in clinical applications. We clarify the statistical theory, and investigate the impact of referencing susceptibility measurements to different regions to facilitate practical implementation and clinical applications.

Keywords: Susceptibility/QSM, Genetic Diseases, Haematology

Motivation: Sickle cell disease (SCD) can lead to cognitive difficulties, but transfusion treatment presents a risk of iron overload which may lead to neurodegeneration. Better understanding of the impact of SCD and transfusions is needed.

Goal(s): To use quantitative susceptibility mapping (QSM) to assess iron deposition in the brain in SCD with and without transfusions.

Approach: Brain susceptibility was quantified in 28 SCD patients and 16 healthy controls using QSM and related to fine motor function by a general linear model.

Results: Susceptibilities in deep brain structures were not correlated with transfusions, SCD status (except in substantia nigra), or motor function (except in pulvinar).

Impact: Using an up-to-date QSM reconstruction pipeline reduced noise and artefacts and revealed correlations of susceptibility with age which were not found previously in these data, confirming the importance of correct coil combination for QSM studies.

Keywords: Susceptibility/QSM, Microstructure, Modelling, chi-separation method

Motivation: χ-separation method relies on assuming a certain relaxometric constant (Dr) calculated as the mean of a group of healthy subjects. Recently, we demonstrated that it is subject-specific.

Goal(s): The goal of this study was to evaluate the correlation between Dr and microstructural metrics obtained from diffusion tensor and diffusion kurtosis imaging (DTI and DKI).

Approach: We regressed between Dr against DTI and DKI diffusion metrics in a cohort of healthy controls.

Results: Results showed a positive correlation with fractional anisotropy and axial diffusivity, and a negative correlation with mean and radial kurtosis.

Impact: Understanding how the relaxometric constant of the χ-separation method (Dr) depends on microstructural diffusion metrics will define its personalization. This, in turn, will impact on how we assess the presence of different magnetic susceptibility sources in the brain.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, Susceptibility separation, Repeatability, Reproducibility, 3T, scan-rescan

Motivation: Susceptibility separation methods aim to separate co-existing myelin and iron contributions. However, their repeatability has not been investigated.

Goal(s): Evaluating repeatability of existing separation methods in brain and comparing their performance.

Approach: Three methods (χ-Sep, χ-SepNet, and APART) were applied to 3T scan-rescan data of 21 healthy subjects, and the resultant dia- and paramagnetic maps were evaluated in white and deep gray matter regions.

Results: Reliability varied by method and region, with many regions showing moderate to good reliability. Average repeatability coefficients were 4 ppb and 8 ppb in white matter and iron-rich deep gray regions, respectively. 

Impact: Susceptibility separation methods showed moderate to good reliability in most brain regions, and sub-voxel changes around 5 ppb might be error. Comparing values reported using different methods might not be straightforward, as the difference between measurements could exceed 15 ppb.

Keywords: Susceptibility/QSM, Quantitative Susceptibility mapping, LoopNet, Bidirectional U-net, QSM dipole inversion

Motivation: Most current deep learning (DL) QSM methods were developed based on U-net, whose performances might not be sufficiently good.  

Goal(s): To proposed a new network baseline for deep learning QSM methods development. 

Approach: We developed a LoopNet, by applying the proposed bidirectional loop and a self-tailored GHPA attention module into a Unet backbone, making better use of the latent information in deep networks.

Results: Simulated and in vivo experiments showed that the propoed LoopNet led to improved results than U-net. 

Impact: This work introduces a novel deep neural network backbone, allowing researchers to develop innovative QSM methods easily by upgrading their original U-net to LoopNet, thanks to the plug-and-play design.

Keywords: Susceptibility/QSM, Susceptibility

Motivation: Important physical parameter, relaxometric constant$$$\;{D_r}$$$, linking magnetic susceptibility to induced transverse relaxation acceleration (i.e.,$$$\;{R2'}$$$) has not yet been fully understood in brain.

Goal(s): To investigate underlying mechanisms affecting relaxometric constant in brain using temperature-dependent relaxometry and susceptibility and explore a better field-strength correction for ultra-high-field MRI.  

Approach: 3T and 7T R2*/R2'/quantitative-susceptibility maps were acquired from a post-mortem brain at different temperatures and analyzed based on the physical model.

Results: In human brain, effects of temperature-dependent water susceptibility, water diffusion, and field strength on D_r were observed, and a field-strength correction coefficient was calculated, generating consistent chi-separation maps at both 3T and 7T.

Impact: A better understanding of relaxometric constant in brain can provide better insight on effects of susceptibility sources (e.g., iron and myelin), on MR relaxometry, improving quantification accuracy of those biological substances using MRI.

Keywords: Non-Proton, Non-Proton, Spectroscopy, carbon-13

Motivation: To develop a safe MR method to non-invasively measure skeletal muscle glycogen levels in humans.

Goal(s): To reduce SAR without degrading the spectral quality of the ¹H-decoupled C1-glycogen peak in ¹³C MRS.

Approach: To introduce the two-pulse phase-modulated (TPPM) ¹H decoupling scheme, which is widely used for ¹³C NMR of organic solids, into the ¹³C MRS pulse sequence for a clinical scanner.

Results: The ¹H-decoupled C1-glycogen peak could be obtained from a solution phantom using a clinical 3T scanner while reducing SAR with shortening the duration of the TPPM ¹H decoupling during ¹³C FID acquisition.

Impact: ¹³C MRS with the TPPM ¹H decoupling for measuring human skeletal muscle glycogen levels may be more advantageous at high magnetic fields due to the lower SAR, leading to higher SNR or shorter scan times.

Keywords: Non-Proton, Non-Proton, 23Na, Sodium, Triple Quantum (TQ)

Motivation: Sodium TQ-signal is potential viable biomarker for cell viability. However, TQ acquisition requires phase-cycling sequences with long scan times, which currently hinder clinical application.

Goal(s): We present a novel method to estimate the TQ-signal directly from the FID without phase-cycling.

Approach: Compare the our method's TQ-signal with the TQTPPI sequence and theoretical prediction. Investigate the impact of noisy data on our method and provide a proof-of-concept imaging sequence.

Results: The TQ-signal of our method was in close agreement with the TQTPPI TQ-signal and the theoretical prediction. Even for low SNR, our method performed well. Proof-of-concept imaging with our method was successfully demonstrated.

Impact: With our method scan time of sodium TQ imaging can be dramatically reduced. This approach may expand TQ imaging applications and thus may leverage the full potential of sodium TQ signal.

Keywords: Deuterium, Deuterium, Deuterium Metabolic Imaging, 7T, human brain, Magnetic Resonance Spectroscopic Imaging

Motivation: Sufficiently high spatial resolution for metabolic mapping of brain glucose metabolism is crucial as regional differences are present in many severe brain diseases, such as dementia, tumors and schizophrenia.

Goal(s): To increase spatial resolution for whole brain deuterium metabolic imaging without prolonging scan times.

Approach: Implement density-weighted concentric ring trajectory for ²H FID-MRSI readout to achieve 2.5-fold increase in spatial resolution while maintaining sufficient SNR. 

Results: Contrast-enhanced metabolic maps were acquired using CRT with significantly higher (+33%,p<0.01) Glx concentrations in GM regions compared to WM, while no differences were observed using lower resolution phase-encoded MRSI. 

Impact: Increased spatial resolution for dynamic deuterium metabolic imaging is crucially needed as many severe brain pathologies feature regional differences in brain glucose metabolism. However, prolonged scan times ultimately limit the achievable spatial resolution using conventional methods for whole brain DMI.

Keywords: Non-Proton, Non-Proton

Motivation: Perfluorooctyl bromide (PFOB) can be used to visualize the inflammatory reaction after myocardial infarction with ¹⁹F MRI, but effective methods for its imaging in large animals in vivo are still missing.

Goal(s): To develop a Hadamard-encoded sequence that removes the chemical shift artifacts of PFOB and increases the ¹⁹F SNR for application in large animal experiments.

Approach: A 3D center-out radial FLASH-sequence was developed and compared to a Cartesian FLASH-sequence in PFOB-phantoms. The radial sequence was tested in a pig after PFOB injection.

Results: Lowering TE increased the SNR by a factor of 2.4, which allowed to reconstruct ¹⁹F images of the animal.

Impact: Hadamard-encoded radial 19F MRI optimally uses the available multi-spectral information of PFOB which makes it the ideal candidate for monocyte tracking in large animals.

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas), multi echo, bSSFP, radial readout

Motivation: 3D Metabolic imaging of hyperpolarized (HP) ¹³C agents demands specialized signal excitation and acquisition strategies.

Goal(s): This study introduces the combination of multi-echo bSSFP and radial readout with a spiral phyllotaxis pattern to rapidly image ¹³C-labeled contrast agents.

Approach: We implemented the novel sequence in a rodent in vivo experiment using HP [1-¹³C]pyruvate.

Results: Employing iterative signal decomposition and radial data reconstruction, we successfully captured the global signal dynamics with an unprecedented temporal resolution of 16 ms. Besides, we generated concentration maps for pyruvate, lactate, alanine, and calculated area-under-the-curve (AUC) metabolite ratio maps for Lac/Pyr and Ala/Pyr.

Impact: Hyperpolarized ¹³C 3D metabolic MRI is challenging due to the short-living magnetization. With 3D spiral phyllotaxis radial multi-echo bSSFP MRI and post-scan metabolite separation, large areas of interest can be acquired and reconstructed into signal time-curves and 3D metabolite maps.

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas), B1 correction, B0 correction

Motivation: B₀ and B₁ inhomogeneities affect signal quantification and kinetic modelling but are challenging to map and correct for in hyperpolarized MRI due to the signal being exogenous and non-renewable.

Goal(s): Develop a fully-integrated B₀ and B₁ mapping method that does not require specialized pulse sequence programming, additional hardware, nor any additional carbon-13 dose.

Approach: Varying echo times and flip angles in the imaging sequence.

Results: The in-vivo field maps agreed well with independently acquired maps and could correct for B0 off-resonance blurring and B₁ inhomogeneity.

Impact: A fully-integrated B₀ and B₁ mapping and correction method for hyperpolarized carbon-13 MRI is presented and validated in vivo. This method is readily implemented and can improve image quality, helping ¹³C metabolic imaging become more robust for clinical studies.

Keywords: Non-Proton, Non-Proton

Motivation: Sodium MRI (²³Na-MRI) holds significant potential, but its clinical use is still limited due to challenges arising from low signal-to-noise ratio (SNR). Balanced steady-state free precession (bSSFP) sequences are particularly suited for ²³Na-MRI, being highly SNR efficient, but there are opportunities to extract more signal components.

Goal(s): We aim to improve SNR in sodium bSSFP acquisitions and produce additional tissue contrasts.

Approach: We propose a strategy to extract additional information from a series of phase-cycled bSSFP images using different linear combinations.

Results: Three different signal components were extracted from phase-cycled bSSFP data and combined. Results showed an SNR boost in fluid.

Impact: This offers a simple way to improve the SNR in sodium MRI images, with potential applications being pathologies that alter biofluid sodium concentrations.

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas)

Motivation: Fully sampled 3DspCSI acquisition limits the temporal resolution for dynamic imaging  

Goal(s): Our goal was to reconstruct highly under-sampled 3DspCSI without significant image artifacts

Approach: We proposed a low rank plus local sparse (LLS) reconstruction with two types of configurations to reconstruct the under-sampled 3DspCSI data

Results: proposed methods with both types of configurations can effectively reduce the image artifacts due to under-sampling. Type 2 configuration performs slightly better than Type 1 with less image artifacts due to the distinct patterns along the slice dimension

Impact: With the proposed LLS reconstruction, an effective acceleration of 4 can be achieved for 3DspCSI without significant image artifacts. The improvement in temporal resolution helps to quantify the metabolite kinetics during a fixed imaging window with hyperpolarized ¹³C agents

Keywords: Deuterium, Deuterium, DMI,MRSI,SSFP

Motivation: DMI's faces a poor SNR, and the detection of vital Glx/lactate metabolites in the brain tumor can be compromised.

Goal(s): This research aims to determine whether the optimized CSI-SSFP imaging method is effective for detecting the four biomarkers (HDO, Glucose, Glx, and Lactate) with improved SNR compared to traditional CSI in rodent brains.

Approach: The approach involves comparing DMI SNR using both traditional CSI and CSI-SSFP for monitoring and imaging the metabolism of injected [6,6’-²H₂]-glucose in healthy mouse brains.

Results: CSI-SSFP highlights substantial enhancement of 2-3 times in SNR for Glx and lactate.

Impact: DMI is promising to assess the Warburg effect associated with cancer. The CSI-SSFP method provides several folds of SNR improvement, which is critical to improve sensitivity and resolution aiming for imaging intra-tumor heterogeneity and metabolic reprograming in brain tumors.

Keywords: Non-Proton, Spectroscopy, Phosphorus, 31P, pH, magnesium, brain

Motivation: The reliability of conventional ³¹P MRS-based methods for the determination of pH and magnesium ion content (Mg) is hampered when applied to pathologies due to their calibration for physiological conditions.

Goal(s): The aim of this study was the advancement of a novel approach for pH and Mg mapping to improve its reliability for application in vivo.

Approach: This advancement was performed by incorporating an additional input parameter into the approach and tested on in vivo ³¹P MRSI brain datasets.

Results: Compared to the original algorithm, the advanced version resulted in robust mapping of pH and Mg yielding homogeneous brain maps for healthy volunteers.

Impact: The advancement of a novel approach for the in vivo determination of pH and magnesium ion content under different chemical conditions improves its reliability and can now potentially be used for the investigation of pathologies such as cancer.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: Manufacturer-supplied transmitter calibrations are unsuitable for ¹²⁹Xe MRI due to the transient nature of its magnetization, but existing ¹²⁹Xe calibration protocols exhibit incomplete spoiling that adversely affects accuracy in flip angle measurements.

Goal(s): We sought to develop a new spoiling-gradient configuration for ¹²⁹Xe MRI transmit calibration that corrects the incomplete spoiling and improves accuracy.

Approach: Spoiling configurations were simulated, tested, and optimized in a water phantom. The optimal configuration was tested in subjects who underwent ¹²⁹Xe MRI with both calibration schemes.

Results: A configuration that increases spoiling-gradient moment with each FID corrected the incomplete spoiling and improved the accuracy of flip angle measurements.

Impact: Implementing a ¹²⁹Xe MRI transmit calibration that increases spoiling-gradient moment with each FID acquisition improves accuracy in flip angle calculations, thereby ensuring consistently optimal image quality for all subjects and advancing the clinical utility of ¹²⁹Xe MRI.

Keywords: Hyperpolarized MR (Non-Gas), Metabolism, carbon-13 imaging, x-nuclei MRI, metabolic imaging, flexible RF coil, CSI

Motivation: For hyperpolarized ¹³C metabolic imaging studies, a challenge is to achieve high temporal resolution without decreasing spatial and/or spectral resolution. 

Goal(s): To accelerate hyperpolarized ¹³C MRI by combining a 2D Chemical Shift Imaging (CSI) sequence with SENSitivity Encoding (SENSE) reconstruction.

Approach: Due to the low natural abundance of ¹³C, the sensitivity maps needed for SENSE reconstruction cannot be pre-acquired. As such, in this work, the novel approach of using sodium sensitivity maps was demonstrated.

Results: SENSE reconstruction corrected aliased images, where in-vivo metabolic information was acquired with a 4-fold temporal acceleration.

Impact: As hyperpolarized ¹³C metabolic imaging is clinically translated, there is a need for easy-to-implement, fast, and robust imaging techniques. Therefore, this study implemented a novel ¹³C technique to accelerate Chemical Shift Imaging: a ubiquitous and robust sequence.

Keywords: Hyperpolarized MR (Gas), Image Reconstruction

Motivation: 3D hyperpolarized ¹²⁹Xe gas exchange imaging is limited by low SNR and long breath-holds, which is problematic for patients with dyspnea and/or low gas transfer. Compressed sensing (CS) reconstruction can accelerate ¹²⁹Xe MRI whilst improving SNR.

Goal(s): To assess whether gas exchange ratio maps are quantitatively preserved with CS dissolved ¹²⁹Xe imaging and investigate the feasibility of reduced-cost natural abundance (NA) CS dissolved ¹²⁹Xe imaging.

Approach: CS-reconstructed gas exchange ratios were evaluated in healthy volunteers and COPD patients and prospectively with NA ¹²⁹Xe.

Results: CS increased image SNR, allowed 3-fold acquisition acceleration and maintained ratio map fidelity, even with NA ¹²⁹Xe.

Impact: Compressed sensing reconstruction of dissolved ¹²⁹Xe spectroscopic imaging improved image quality even with decreased scan time, whilst preserving key gas exchange metrics. This will benefit patients with breathlessness and/or low gas transfer and enables natural abundance dissolved ¹²⁹Xe imaging.

Keywords: Deuterium, Deuterium

Motivation: Abdominal imaging of orally-administered deuterium-labelled tracers can be hindered by artifacts arising from excessive stomach signal.

Goal(s): To establish and optimize methods for acquisition of abdominal deuterium metabolic imaging in conjunction with orally-administered tracers.

Approach: A flexible transmit-receive surface coil was used to image naturally abundant deuterium in healthy volunteers and orally-administered D₂O in a patient with renal cancer.

Results: Water and lipid peaks were repeatably fit with high confidence both in unlocalised spectra and voxels extracted from MRSI in the liver, kidney, and spleen. Artifacts were minimal even 12 minutes after tracer ingestion.

Impact: Feasibility of abdominal deuterium imaging at 3T was demonstrated using a flexible surface coil.  We obtained consistent water measurements in healthy volunteers and good images in a patient with a left-sided renal tumour even just 12 min after drinking D₂O.

Keywords: Non-Proton, Non-Proton

Motivation: Motivation is to unleash the clinical potential of sodium (²³Na) MRI.

Goal(s): Main goal is to answer the key question about what the optimal sequence encoding is?

Approach: 3D sodium sampling schemes were designed, implemented and compared in simulations and experimentally in the human brain and porcine abdomen.

Results: (1) While encoding schemes differ in sampling efficiency, 15ms-Density-Adapted Radial is SNR optimal.
(2) Clinically reasonable acquisition parameters are: total scan time ~10min., nominal matrix size=80³, readout duration=15ms, TR=30ms, flip angle=60°.

Impact: Sodium MRI holds great clinical potential for diagnosing and monitoring of stroke, cancer, etc. Devising and comparing the optimal acquisition will help the sodium field to improve SNR, hence facilitating clinical studies and adoption.

Keywords: Deuterium, Deuterium, FDG-PET

Motivation: The regulation of brain glucose metabolism by GLP1-1R has not been fully verified. 

Goal(s): To explore feasibility of dynamic DMRS in mice brain, and the physiological role of GLP-1R in mouse brain glucose metabolism. 

Approach: we apply DMRS and FDG-PET to quantify dynamic cerebral glucose change, and combine with rs-fMRI to investigate changes in whole-brain functional connectivity. 

Results: GLP-1R KO mice exhibit impaired brain glucose metabolism and central nervous system intolerance to high doses of exogenous glucose.  And the functional brain connectivity in GLP-1R KO mice was significantly lower than that in WT group.

Impact: The decline in functional connectivity may hinder the coordination of work and information transmission between brain regions, thus inhibit normal metabolic regulatory processes. These findings provide a theoretical basis for the treatment strategies of disorders related to brain glucose metabolism

Keywords: Non-Proton, Metabolism, Migraine, 31P Spectroscopy, Preclinical, Central Sensitization, Ultra-high field

Motivation: Migraine is a disorder of neuronal hyperexcitability, but previous work has not been able to capture energetic processes non-invasively during active central sensitization, only after or between migraine attacks. 

Goal(s): This preclinical study evaluates whole brain energetic metabolism and remodeling during a nitroglycerin-induced migraine attack.

Approach: ³¹P spectroscopy using ISIS was used to measure phosphocreatine and ATP levels at baseline and then over a 3-hour period post-NTG administration.

Results: Most notable is the increase in phosphocreatine compared to baseline and controls, as well as an increase in ATP compared to baseline. Both indicate energetic remodeling during central sensitization prior to migraine pain onset.

Impact: Increased phosphocreatine and ATP over the entire brain demonstate significant energetic fluxes during cerebral central sensitization and prior to nociception. This energetic remodeling informs understanding of fundamental migraine pathophysiology and its timing, potentially impacting the administration of potential clinical interventions.

Keywords: Non-Proton, Liver, X-Nuclei, 23Na MRI, Sodium, Ultrahigh Field, 7T, Tissue sodium concentration

Motivation: A scarcity in literature values for the tissue sodium concentration (TSC) in the healthy liver complicates the evaluation of the TSC in the diseased liver.

Goal(s): This study aimed to establish TSC levels in one healthy liver on multiple days to explore potential concentration variations.

Approach: The TSC was assessed using B₁ field corrected and respiratory-sorted quantitative ²³Na MRI.

Results: The TSC values obtained in the healthy liver remained stable over a week and aligned with existing literature values.

Impact: The study's finding of a consistent tissue sodium concentration (TSC) over time in one healthy liver is a valuable insight. It indicates that changes in liver TSC might be accurately linked to diseases, which could improve diagnosis of liver diseases.

Keywords: Deuterium, Deuterium, Spectroscopy, Metabolism

Motivation: Most Deuterium Metabolic Imaging (DMI) studies have employed doubly labelled D₂-glucose, but fully labelled D₇-glucose produces higher deuterium concentrations in the brain, providing higher signal-to-noise-ratio measurements and additional information about metabolism.

Goal(s): We carried out a detailed comparison of 7T DMI measurements in the brain in 15 participants who ingested either D₇-glucose or D₂-glucose.

Approach: 3D ²H CSI data was acquired at 7T at natural abundance and then every 15 minutes for ~65- minutes following ingestion of 0.75 g/kg of labelled glucose.

Results: Larger signals and concentrations were measured following D₇-glucose ingestion, D₇/D₂ signal ratios were explained by differing numbers of labels.

Impact: Deuterium metabolic imaging (DMI) using labelled glucose forms a powerful tool for mapping glucose metabolism. D₇-glucose produces higher deuterium concentrations in the brain, providing a higher signal-to-noise-ratio that would be valuable in studies of metabolism in health and disease.

Keywords: Non-Proton, Non-Proton

Motivation: To improve understanding of sodium and water balance in haemodialysis patients.

Goal(s): To study sodium stores in leg muscle and skin in younger and older healthy individuals, and haemodialysis patients, and to assess sodium and water changes following a single haemodialysis session.  

Approach: Sodium (²³Na) MRI of calf skin and muscle in younger older and haemodialysis(HD) patients. ²³Na MRI, and ¹H mDIXON and T₂ relaxometry to study sodium and water content to haemodialysis.

Results: Haemodialysis led to a significant reduction in muscle sodium whilst skin sodium showed little detectable change, ¹H muscle T₂ values showed a significant reduction. 

Impact: Sodium (²³Na) MRI of muscle allows the study of sodium storage with age and in dialysis patients. ²³Na and proton (¹H) T₂ mapping enable the assessment of changes in sodium storage and fluid status in haemodialysis patients.

Keywords: Non-Proton, Non-Proton, Brain Tumours, Sodium Imaging, Multiple Quantum Filteres, Compressed Sensing

Motivation: Leverage cutting-edge enhanced simultaneous single and triple quantum filtered sodium imaging sodium imaging (eSISTINA) at 7T for unparalleled image precision, enhancing diagnostic efficacy and pushing the clinical frontier in brain tumour analysis.

Goal(s): Optimise imaging and relaxometry performance of the eSISTINA sequence without compromising clinically applicability due to exessive measurement times.

Approach: FLORET spiral trajectories coupled with pseudo-randomised undersampling and compressed sensing reconstruction yield significantly enhanced image quality and relaxometry performance of eSISTINA.

Results: Compressed sensing reconstructed images of a brain tumour patient highlight substantial improvements in quality and aquicistion efficiency of eSISTINA at 7T, surpassing prior work at lower field strengths.

Impact: This study demonstrates clearly that eSISTINA at ultra-high field strength is a promising diagnostic tool, offering invaluable insights for clinicians and researchers. Future patient cohort studies will undoubtedly reveal novel perspectives on brain tumours and metabolism.

Keywords: Deuterium, Deuterium, Dynamic 2D fitting; Deuterium metabolic imaging; Brain; 7T

Motivation: Dynamic deuterium metabolic imaging (DMI) data are currently evaluated by first fitting the spectral and then the temporal domain (1D), leading to great fit uncertainty. This might be improved by fitting both domains simultaneously (2D).

Goal(s): To compare dynamic 2D-fitting of time-resolved 3D-DMI data of the human brain and compare its performance to conventional 1D-fitting.

Approach: Simulated and in vivo DMI data were fitted using 1D- and 2D-fitting algorithms and results were compared in terms of precision and accuracy.

Results: 2D-fitting yielded higher precision and accuracy than 1D-fitting for simulated DMI data. For in vivo data, both fitting approaches yielded similar results.

Impact: Improving fitting accuracy to estimate the underlying metabolic kinetics from dynamic deuterium metabolic imaging (DMI) data is crucial, while establishing DMI towards clinical application. 2D-fitting approaches (simultaneous spectral and temporal fitting) could potentially improve overall robustness of the methodology.

Keywords: Deuterium, Cancer, Preclinical

Motivation: Diffuse midline gliomas (DMGs) are devastating pediatric brain tumors. Although MRI is the mainstay for DMG imaging, it does not reliably report on response to therapy.

Goal(s): The goal of this study was to assess the utility of deuterium metabolic imaging for DMGs.

Approach: To this end, we interrogated [6,6’-²H]-glucose metabolism in patient-derived and syngeneic models.

Results: [6,6’-²H]-glucose enables non-invasive visualization of the metabolically active tumor lesion in mice bearing intracranial DMGs. Importantly, [6,6’-²H]-glucose provides an early readout of response to targeted therapy in vivo. Collectively, our studies highlight the potential of [6,6’-²H]-glucose for imaging tumor burden and response to therapy in DMGs.  

Impact: Diffuse midline gliomas are deadly childhood brain tumors. Using clinically relevant patient-derived and murine tumor models, we show that deuterium metabolic imaging using [6,6’-2H]-glucose enables non-invasive assessment of tumor burden and early response to therapy in diffuse midline gliomas.

Keywords: Deuterium, Metabolism

Motivation: Deuterium metabolic imaging (DMI) might permit mapping of cardiac metabolism by MRI.

Goal(s): To port DMI tools developed at 11.7T for mice to 3T, and develop methods for cardiac DMI.

Approach: Simulations, phantoms, and in vivo studies were conducted to measure SNR at 3T, develop an optimized protocol, and account for B0 inhomogeneity.

Results: At 11.7T, cardiac DMI was tested in a control mouse. At 3T, phantom studies showed that multi-echo bSSFP methods yield increased SNR vs. GRE.  B0-mapping helps in isolating the metabolites in phantoms. 

Impact: Development of DMI tools for use in cardiac DMI at clinical field strengths.

Keywords: Deuterium, Deuterium, Alzheimer's Disase

Motivation: Impaired brain energy metabolism at early stage is found to be the driving factor of Alzheimer’s Disease (AD) progression.

Goal(s): The study aim to investigate the potential of using deuterium magnetic resonance imaging to characterize the glucose metabolism in AD mouse model.

Approach: Deuterium magnetic resonance spectroscopic imaging with the administration of [2,3,4,6,6’-²H₅]-D-Glucose in 5xFAD and C57 mice.

Results: Our preliminary results indicate higher glutamine/glutamate (Glx) production rate in 5xFAD mice compared to normal mice, especially in the hypothalamus region. 

Impact: Our work may shed light on developing new method in the early detection of AD based on the glucose metabolism abnormality.

Keywords: Non-Proton, Metabolism

Motivation: Brain sodium (²³Na) MRI can provide sodium concentration information in vivo, but there are still some challenges, such as low SNR and relatively low resolution.

Goal(s): To assess the reproducibility of total sodium concentration (TSC) evaluation  in the putamen and substantia nigra of healthy individuals using 3D ²³Na MRI.

Approach: Ten healthy subjects were scanned twice consecutively using the 3D TFE UTE and T1W sequence to quantify the TCS in the putamen and substantia nigra. The reproducibility was evaluated.

Results: Concentration of sodium in phantoms can be accurately quantified and TSC in putamen, substantia nigra had good consistency for ²³Na MRI.

Impact: ²³Na-MRI shows potential in becoming a stable and useful biomarker for the diagnosis of patients with neurodegenerative diseases.

Keywords: Deuterium, Deuterium

Motivation: The inherently low SNR of DMI hinders clinical viability at 3T.  

Goal(s): We evaluate an anatomically guided reconstruction (AGR) approach to enhance the spatial resolution of DMI scans via exploiting correlated anatomic information in corresponding ¹H images.

Approach: We used segmented MRI scans of patients with CNS tumors to simulate DMI metabolic maps and corresponding ground truth, which were then used to evaluate AGR performance with respect to both SNR and the targeted spatial resolution.  

Results: Findings demonstrated that this AGR approach is largely robust to noise and most successful at upsampling factors between 2-4, after which the reconstructions starts to fail.

Impact: DMI can uncover novel metabolic information about CNS lesions. We demonstrate that mutual anatomic information from ¹H MRI can bring 3T DMI closer to clinically-viable spatial resolutions. Further work is needed to assess its utility across lesion sizes and pathologies.

Keywords: Deuterium, Deuterium, Preclinical

Motivation: Effective treatment response seen in paediatric-type diffuse high grade glioma with conventional MRI can take months to manifest.

Goal(s): Evaluation of ²H-MRS for monitoring the metabolism of deuterated glucose in PDHGG cells and assessing early metabolic response to PI3K inhibition.

Approach: PIK3R1 mutant neurospheres were treated with a dual PI3K/mTOR inhibitor for 72 and 24 hours, and ²H spectra dynamically acquired in the presence of [6,6-²H₂]-glucose.

Results: Treatment significantly reduced glycolytic rates at both timepoints. At 24 hours there was no difference in cell number or viability, highlighting the potential of ²H-MRS to provide an early biomarker of response.

Impact: Establishing acute treatment-induced changes in the glycolytic rate of PDHGG neurospheres using 2H-MRS provides confidence in the sensitivity of deuterium metabolic imaging for assessing the early response of orthotopic PDHGG models to PI3K inhibition in vivo.

Keywords: Deuterium, Deuterium

Motivation: Glioma tumor cells have abnormally higher uptake of methionine, compared to normal brain tissues.

Goal(s): To characterize the methionine preference of glioma cells through deuterium magnetic resonance spectroscopy.

Approach: Deuterium magnetic resonance spectroscopy in glioma C6 and CTX-TNA2 glial cells incubated by [1-²H₃]-methionine

Results: Abnormal uptake of deuterated methionine in glioma cells was revealed by using magnetic resonance deuterium spectroscopy, compared to normal cells

Impact: Deuterium magnetic resonance imaging with deuterium labeled methionine may have the potential in accurate diagnosis and treatment assessment of glioma.

Keywords: Non-Proton, Preclinical, Gelatin scaffolds, 19F MRI/MRS

Motivation: Gelatin-based scaffolds may be seeded by cells or may serve as depots for drugs and ensure their slow release.

Goal(s): The goal of the study was to prepare scaffolds with tunable properties and monitor their stability in time in a mouse model in vivo.

Approach: The scaffolds implanted to mice were monitored by ¹H/¹⁹F MRI, fluorine content was quantified by ¹⁹F MR spectroscopy.

Results: The scaffolds can be easily monitored by ¹⁹F MRI/MRS. The study confirmed that the design of the scaffolds can be fine-tuned for future applications, biodegradation rates may be set from several weeks up to one year.

Impact: Gelatin-based scaffolds pave the road towards qualitatively different drug applications and regenerative medicine. The study evaluated their applicability, traceability by ¹H/¹⁹FMRI, and stability in vivo. Future work should investigate release speed of different compounds (drugs) both hydrophilic and hydrophobic.

Keywords: Deuterium, Deuterium, Relaxation Times, Brain, 7T, Deuterium Metabolic Imaging

Motivation: Deuterium metabolic imaging (DMI) is an emerging Magnetic Resonance technique to non-invasively map the cellular glucose uptake and downstream metabolism. For a reliable concentration estimation, tissue-specific relaxation times are essential, yet only unlocalized relaxation time constants of deuterium labeled resonances are reported. 

Goal(s): Measure tissue-specific relaxation times of deuterated resonances (glucose, glutamate+glutamine).

Approach: Inversion recovery and Hahn spin-echo acquisition schemes were implemented into 3D FID ²H-MRSI using concentric ring trajectory readout.

Results: Measured T₁ and T₂ relaxation time constants of Glc (T₁^GM=56±14ms; T₁^WM=60±19ms; T₂^GM=37±1ms; T₂^WM=36±2ms) and Glx (T₁^WM=167±22ms; T₁^GM=173±12ms; T₂^GM=36±1ms; T₂^WM=34±1ms) were not significantly different between GM and WM.